Effect of Epinephrine on Central Nervous System and Cardiovascular System Toxicity of Bupivacaine in Pigs

To determine what effect the addition of epinephrine has on bupivacaine toxicity, toxic doses of bupivacaine were administered to awake spontaneously breathing pigs. Twenty animals were randomized to one of two groups. One group received an infusion of bupivacaine with epinephrine (5 micrograms/ml) at a rate of 2 mg.kg-1.min-1; the other received an infusion of plain bupivacaine at the same rate. Bupivacaine infusion was continued until cardiovascular collapse. Following cardiovascular collapse we attempted to resuscitate the animals via open chest cardiac massage and a standardized resuscitation protocol. The addition of epinephrine to bupivacaine significantly increased blood pressure and systemic vascular resistance but not heart rate or cardiac output early in the bupivacaine infusion. Epinephrine had no effect on the dose of bupivacaine that caused cardiovascular collapse (P = 0.1), on the plasma concentration of bupivacaine at collapse (P = 0.9), or on the ability to resuscitate animals following cardiovascular collapse. The addition of epinephrine decreased the dose of bupivacaine required to initiate cardiac dysrhythmias (P = 0.003). The first dysrhythmia experienced by the epinephrine group was second degree heart block, which contrasts with the premature ventricular and atrial dysrhythmias experienced by the plain group. The dose of bupivacaine that produced seizures was also reduced by the addition of epinephrine (P = 0.006). The addition of epinephrine to bupivacaine did not alter the dose of bupivacaine that caused cardiovascular collapse in awake spontaneously breathing pigs but did decrease the dose of bupivacaine that caused seizures and dysrhythmias.