CENTRAL-NERVOUS-SYSTEM TOXICITY OF LOCAL-ANESTHETIC MIXTURES IN THE RAT

Local anesthetics are often administered as mixtures during regional a nesthesia. This study investigated whether a synergistic or antagonist ic interaction between amide/amide or amide/ester local anesthetic com binations is present with respect to central nervous system toxicity. For surgical preparation, rats were anesthetized with 0.8% halothane i n 30% O2/balance N2O and mechanically ventilated. Mean arterial blood pressure and the electroencephalogram were continuously monitored. Aft er surgery, the halothane was discontinued for 15 min. An intravenous infusion of solutions containing lidocaine alone, bupivacaine alone, o r any of three mixtures of the two drugs was then begun and continued at a fixed rate until seizure activity was observed on the electroence phalogram. Total administered doses of both drugs were compared by iso bolographic analysis. After a similar protocol, a second experiment wa s performed evaluating lidocaine, tetracaine, or any of three mixtures of those two drugs. In both experiments, normocapnia, normoxia, and n ormothermia were maintained for all rats. For of lidocaine/bupivacaine (P = 0.40) and lidocaine/tetracaine (P = 0.24), there was no evidence that a significant degree of either synergism or antagonism was prese nt. At the onset ot seizures, mean arterial pressure was lowest in the lidocaine-alone groups in both experiments. Increasing doses of eithe r bupivacaine or tetracaine (with correspondingly decreasing doses of lidocaine) were associated with greater mean arterial pressure values at onset of seizures. We conclude that central nervous system toxic ef fects of amide/amide or amide/ester anesthetic combinations, such as m ight occur during accidental intravascular injection, are no more than when the drugs are administered alone. Because such combinations appe ar to have additive epileptogenic effects, proportional reductions in the dose of one drug must be made if administered in combination with another.