Acute cardiovascular and central nervous system toxicity of bupivacaine and desbutylbupivacaine in the rat

Desbutylbupivacaine, a major metabolite of bupivacaine, is known to accumulate during long-term continuous infusion blocks in man. Its acute toxicity in comparison with that of bupivacaine has not been studied. In a lightly anaesthetized rat model, bupivacaine (2 mg/kg/min, N = 10) or desbutylbupivacaine (4 mg/kg/min, N = 10) was infused i.v. until asystole. Arterial blood pressure, ECG and EEG were continuously recorded. The mean doses of bupivacaine producing cardiac toxicity, i.e. arrhythmia (12.4 mg/kg) and asystole (24.0 mg/kg), were approximately half of those of desbutylbupivacaine. Seizure activity on the EEG was observed in only one of the desbutylbupivacaine-infused rats while all rats receiving bupivacaine developed seizures (mean dose 5.2 mg/kg). Desbutylbupivacaine infusion caused a decrease in arterial blood pressure greater than that resulting from bupivacaine infusion. When desbutylbupivacaine 0.67 mg/kg/min was coinfused with bupivacaine 2 mg/kg/min, the cardiovascular toxicity of bupivacaine was clearly potentiated. The EEG parameters were affected in a similar fashion as when bupivacaine alone was infused. In this rat model, desbutylbupivacaine was about half as toxic as bupivacaine judged by cardiac parameters, and clearly less toxic to the central nervous system than bupivacaine.