Rosenberg P H, Heavner J E
Department of Anaesthesiology, Helsinki University Central Hospital, Finland.
Acta Anaesthesiol Scand. 1992 Feb;36(2):138-41. doi: 10.1111/j.1399-6576.1992.tb03440.x.
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.
去丁布比卡因是布比卡因的一种主要代谢产物，已知在人体长期持续输注阻滞过程中会蓄积。其与布比卡因相比的急性毒性尚未得到研究。在轻度麻醉的大鼠模型中，静脉输注布比卡因（2mg/kg/min，N = 10）或去丁布比卡因（4mg/kg/min，N = 10）直至心搏停止。连续记录动脉血压、心电图和脑电图。产生心脏毒性（即心律失常，12.4mg/kg）和心搏停止（24.0mg/kg）的布比卡因平均剂量约为去丁布比卡因的一半。在输注去丁布比卡因的大鼠中仅1只观察到脑电图上的癫痫活动，而所有接受布比卡因的大鼠均出现癫痫发作（平均剂量5.2mg/kg）。输注去丁布比卡因引起的动脉血压下降大于输注布比卡因所致。当0.67mg/kg/min的去丁布比卡因与2mg/kg/min的布比卡因联合输注时，布比卡因的心血管毒性明显增强。脑电图参数的变化方式与单独输注布比卡因时相似。在该大鼠模型中，根据心脏参数判断，去丁布比卡因的毒性约为布比卡因的一半，且对中枢神经系统的毒性明显低于布比卡因。
