Yanxin Cheng1, Hong Li2, Jun Li3, Yongxue Chen4, Ran Duan1, Jinge Yuan4, Senming Zhao5. 1. Pain Medicine Center, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China. 2. Department of Anesthesiology, The Fourth Hospital of Shijiazhuang, Shijiazhuang, Hebei, China. 3. Department of Anesthesiology, Kailuan General Hospital, Tangshan, Hebei, China. 4. Department of Anesthesiology, Handan Center Hospital, Handan, Hebei, China. 5. Pain Medicine Center, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China. senming63@163.com.
Abstract
PURPOSE: KCNQ2/3 channels play an important role in controlling neuronal excitability. Agents that decrease KCNQ2/3 current amplitudes are proconvulsant, whereas KCNQ2/3 current enhancers are anticonvulsant. Levobupivacaine is able to block the KCNQ2/3 channels and enhance neuronal excitation, whereas retigabine is able to reopen the channels and thus reduce overexcitation of neurons. In this study, we aimed to determine if retigabine is able to abolish local-anesthetic-induced seizures. METHODS: Twenty New Zealand rabbits were randomly divided into two groups of ten. Levobupivacaine (0.5 %) was infused into conscious rabbits via the marginal ear vein at 8 ml/kg/h until the rabbits seized, and 5 mg/kg of retigabine were injected intravenously to terminate the seizure. The corresponding volume of saline was used as a control. The behavior of and the electroencephalogram (EEG) for each rabbit were continually monitored. Before levobupivacaine infusion, the rabbits were placed in a prostrate position calmly on the experimental platform, and the EEG pattern exhibited β waves. Intravenous levobupivacaine induced a typical EEG seizure characterized by multiple spike and slow wave complexes. The EEG changes were accompanied by behavioral convulsions which were characterized by clonic activity and opisthotonus. RESULTS: Retigabine effectively terminated the electrographic and behavioral seizures. After receiving 5 mg/kg of retigabine, the animals became drowsy, and the EEG changed to δ waves. CONCLUSIONS: We propose that KCNQ2/3 channels play an important role in levobupivacaine-induced central nervous system toxicity, and a KCNQ2/3 channel activator may be used to treat levobupivacaine-induced convulsions.
PURPOSE:KCNQ2/3 channels play an important role in controlling neuronal excitability. Agents that decrease KCNQ2/3 current amplitudes are proconvulsant, whereas KCNQ2/3 current enhancers are anticonvulsant. Levobupivacaine is able to block the KCNQ2/3 channels and enhance neuronal excitation, whereas retigabine is able to reopen the channels and thus reduce overexcitation of neurons. In this study, we aimed to determine if retigabine is able to abolish local-anesthetic-induced seizures. METHODS: Twenty New Zealand rabbits were randomly divided into two groups of ten. Levobupivacaine (0.5 %) was infused into conscious rabbits via the marginal ear vein at 8 ml/kg/h until the rabbits seized, and 5 mg/kg of retigabine were injected intravenously to terminate the seizure. The corresponding volume of saline was used as a control. The behavior of and the electroencephalogram (EEG) for each rabbit were continually monitored. Before levobupivacaine infusion, the rabbits were placed in a prostrate position calmly on the experimental platform, and the EEG pattern exhibited β waves. Intravenous levobupivacaine induced a typical EEG seizure characterized by multiple spike and slow wave complexes. The EEG changes were accompanied by behavioral convulsions which were characterized by clonic activity and opisthotonus. RESULTS:Retigabine effectively terminated the electrographic and behavioral seizures. After receiving 5 mg/kg of retigabine, the animals became drowsy, and the EEG changed to δ waves. CONCLUSIONS: We propose that KCNQ2/3 channels play an important role in levobupivacaine-induced central nervous system toxicity, and a KCNQ2/3 channel activator may be used to treat levobupivacaine-induced convulsions.
Entities:
Keywords:
KCNQ2/3 channels; Local anesthetic toxicity; Retigabine; Seizure
Authors: J E de La Coussaye; J J Eledjam; P Peray; P Bruelle; J Y Lefrant; B Bassoul; G Desch; J P Gagnol; A Sassine Journal: Br J Anaesth Date: 1993-10 Impact factor: 9.166