Dexmedetomidine Decreases the Convulsive Potency of Bupivacaine and Levobupivacaine in Rats: Involvement of α2-Adrenoceptor for Controlling Convulsions

Abstract

Dexmedetomidine, a highly selective alpha(2)-adrenoceptor agonist, is used in combination with local anesthetics for sedation and analgesia. We tested the hypothesis that dexmedetomidine used for sedation alters the convulsive potency of racemic bupivacaine and levobupivacaine in awake, spontaneously breathing rats. In the first experiments, male Sprague-Dawley rats were randomly divided into six groups: bupivacaine with no dexmedetomidine (bupivacaine control; BC), bupivacaine with small-dose dexmedetomidine (BS), bupivacaine with large-dose dexmedetomidine (BL), levobupivacaine with no dexmedetomidine (levobupivacaine control; LC), levobupivacaine with small-dose dexmedetomidine (LS), and levobupivacaine with large-dose dexmedetomidine (LL) (n = 10 for each group). Continuous infusion of dexmedetomidine (Groups BC and LC, 0 microg x kg(-1) x h(-1); Groups BS and LS, 3.6 microg x kg(-1) x h(-1); and Groups BL and LL, 10.8 microg x kg(-1) x h(-1)) was started after bolus injection (Groups BC and LC, 0 microg/kg; Groups BS and LS, 0.5 microg/kg; and Groups BL and LL, 1.5 microg/kg). Fifteen minutes after the start of the dexmedetomidine infusion, continuous infusion of bupivacaine (Groups BC, BS, and BL) or levobupivacaine (Groups LC, LS, and LL) at 1 mg x kg(-1) x min(-1) was started and continued until tonic/clonic convulsions occurred. Dexmedetomidine achieved significantly different sedation levels both in Groups BC, BS, and BL and in Groups LC, LS, and LL (P < 0.05). Convulsive doses of bupivacaine and levobupivacaine were significantly larger in Groups BL and LL than in Groups BC and LC, respectively (P < 0.01 for both). Concentrations of bupivacaine and levobupivacaine in plasma and in brain at the onset of convulsions were also larger in Groups BL and LL than in Groups BC and LC (P < 0.01 for both). In the second experiment, yohimbine (1 mg/kg) administered 10 min before and 5 min after the start of dexmedetomidine infusion completely reversed the sedative effect of dexmedetomidine (bolus 1.5 microg/kg, followed by 10.8 microg x kg(-1) x h(-1)). Convulsive doses and plasma and brain concentrations of bupivacaine and levobupivacaine at the onset of convulsions in rats receiving yohimbine and dexmedetomidine were significantly smaller than in those receiving only dexmedetomidine (P < 0.05 for all) and were similar to those without dexmedetomidine or yohimbine. We conclude that dexmedetomidine used for sedation decreases the convulsive potency of both bupivacaine and levobupivacaine in rats. Alpha(2)-adrenoceptor agonism may be involved in this anticonvulsant potency.

Dexmedetomidine for sedation during electroencephalographic analysis in children with autism, pervasive developmental disorders, and seizure disorders

“…Dexmedetomidine (doses of 10 and 100 μg/kg, but not one μg/kg) also reduced the seizure threshold during enflurane anesthesia in cats [20]. Anticonvulsant effects were shown by other investigators [21,22]. Dexmedetomidine (20 μg/kg followed by an infusion of one μg kg -1 min -1 ) increased the dose of cocaine required to cause seizures in Sprague-Dawley rats [21].…”

“…With a cocaine infusion at 1.25 mg/kg per minute, rats treated with dexmedetomidine manifested seizures at 49.3 ± 14.8 minutes versus 25.0 ± 7.7 minutes in controls. In Sprague-Dawley rats, the dose of either levobupivacaine or bupivacaine required to induce seizures was higher in rats treated with dexmedetomidine than in controls [22].…”

“…The literature regarding the potential anticonvulsant or proconvulsant effects of dexmedetomidine are mixed [19][20][21][22]. A lowering of the seizure threshold (proconvulsant effect) with doses of 100 and 500 μg/kg, but not 20 μg/kg, was noted in rats treated with the epileptogenic agent, pentylenetetrazol [19].…”

Pretreatment with Dexmedetomidine or Thiopental Decreases Myoclonus after Etomidate: A Randomized, Double-Blind Controlled Trial

“…It was hypothesized that the reason for the excitatory phenomenon of myoclonus was a disequilibrium of the drug at the various effect sites in the central nervous system (CNS) [9,10]. Tanaka et al showed that dexmedetomidine administered for sedation reduced the convulsive potency of bupivacaine and levobupivacaine in awake, spontaneously breathing rats, probably by a 2 -adrenoceptor agonism [11]. Although myoclonus is thought not to be generated by an epileptic focus, dexmedetomidine, which acts to reduce the severity of convulsions, has not been previously investigated for myoclonus induced by etomidate.…”

Repeated dexmedetomidine infusions, a postoperative living-donor liver transplantation patient

“…Liver dysfunction may occur postoperatively in living-donor liver transplantation (LDLT) patients, as only 50% of the standard liver volume is usually transplanted to the recipient, and hypoperfusion and rejection of the graft or tissue can occur. Here we report the case of an LDLT previously reported method [7]. The lower limit of DEX quantitation was 50 pmol·ml −1 , and the intraassay and interassay variations were less than 8% throughout the range (50-5000 pmol·ml −1 ).…”