Bupivacaine, an amide type local anesthetics, is frequently used for various type of regional anesthesia. Numerous in vivo and in vitro studied have examined the examined the cardiotoxicity of bupivacaine by intravenous injection.
Bupivacaine overdose induced cardiac toxicity and directly depressed both cardiac electrophysiology and hemodynamic status. Several reports, however, indicate a participation of the CNS in cardiac toxicity of bupivacaine.
Clonidine, an imidazolin α2-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 occurrence 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, heart rate and invasive arterial blood pressure were continuously recorded. Clonidine 5μg/Kg
(Clonidine
group), midazolam 0.3mg/Kg (Midazolam group) or saline (Saline group) was injected intravenously in randomized fashion. After 10 min, and intravenous infusion of bupivacaine was started at 1mg/Kg/min. The time of occurrence 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.
@ES The results were as follows.
@EN 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 significantly reduced in the Clonidine and the Midazolam groups (P<0.01, P<0.05).
2) Following the start the 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 Midazolam groups than in the Saline group. The time to 25% reduction in baseline 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 siginficantly different between the groups.
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