| Effects of Clonidine and Midazolam Pretreatment on Cardiovascular Toxicity of Intravenous Bupivacaine in Rabbits. |
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Chi Hyo Kim, Jong Hak Kim, Choon Hi Lee |
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Department of Anesthesiology, College of Medicine, Ewha Womans University, Seoul, Korea. |
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| Abstract |
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Bupivacaine, an amide type local anesthetics, is frequently used for various type of re- gional anesthesia. Numerous in vivo and in vitro studied have examined the cardiotoxicity of bupivacaine by intravenous injection. Bupivacaine ovsrdose induced cardiac toxicity and directly depressed both eardiac electrophysiology and hemodynamie status.
Several reports, however, indicate a participation of the CNS in cardiac toxicity of bupivacaine. Clonidine, an imidazolin alpha2-adrenoreceptor agonist, given prophylactically delays the toxic manifestation of bupivacaine overdose and dose not accentuate the subsequent hypotension. Benzodiazepine, such as midazolam for anxiolytics prior to regional anesthesia, raise the seizure threshold, delay the occurence of CNS toxicity, and increase the threshold of cardiac toxicity. Eighteen rabbits(six in each group) were anesthetized with pentobarbital, and controlled ventilation was started with room air.
Electrocardiogram, hesrt rate and invasive srterial blood pressure were continuously recorded. Clonidine 5 ug/Kg(Clonidine group), midazolam 0. 3mg/Kg(Midazolam group) or saline(Saline group) was injected intravenously in randomized fashion. After 10 min, an intravenous infusion of bupivacaine was started at 1mg/Kg/min. The time of occurence of the bupivacaine induced toxic events(first QRS modification, first dysrhythmia, 25 and 50% reduction in baseline heart rate and mean arterial pressure, and asystole) was recorded. The results were as follows. 1) After pretreatment, the changes of heart rate were significantly reduced in the Clonidine group(P<0.01), but the changes of mean arterial pressure were signifieantly reduced in the Clonidine and the Midazolam groups(P<0.001, P<0.05). 2) Following the start of bupivacaine infusion, the time to the onset of QRS modification was significantly longer in the Midazolam group than in the Saline group, and the times to the onset of dysrhythmia, 25 and 50% reduction in baseline heart rate, each, were significantly longer in the Clonidine and the Midazolsm groups than in the Saline group. The time to 25% reduction in ine mean arterial pressure was significantly longer in the Clonidine group compared to the Saline group, but not in the Midazolam group, and the time to 50% reduction baseline mean arterial pressure and asystole, each, were increased according to the order of the Saline, the Midazolam and the clonidine groups, and significantly different between the groups. |
| Key Words:
Bupivacaine; Clonidine; Midazolam; Cardiotoxicity |
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