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.