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Effectiveness of retigabine against levobupivacaine-induced central nervous system toxicity: a prospective, randomized animal study

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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.

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Acknowledgments

We would like to thank Chen Xu from the EEG Center for her help in EEG examinations. We would also like to thank Zhenshan Zeng and Tao Li from the Center for Animal Experiment of the Third Hospital of Hebei Medical University for their assistance with the study. This work was supported by The Science & Technology Supporting Program of Hebei Province (grant no: 092061112D).

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Authors and Affiliations

  1. Pain Medicine Center, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China

    Yanxin Cheng, Ran Duan & Senming Zhao

  2. Department of Anesthesiology, The Fourth Hospital of Shijiazhuang, Shijiazhuang, Hebei, China

    Hong Li

  3. Department of Anesthesiology, Kailuan General Hospital, Tangshan, Hebei, China

    Jun Li

  4. Department of Anesthesiology, Handan Center Hospital, Handan, Hebei, China

    Yongxue Chen & Jinge Yuan

Authors
  1. Yanxin Cheng
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  2. Hong Li
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  3. Jun Li
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  4. Yongxue Chen
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  5. Ran Duan
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  6. Jinge Yuan
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  7. Senming Zhao
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Corresponding author

Correspondence to Senming Zhao.

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Cheng, Y., Li, H., Li, J. et al. Effectiveness of retigabine against levobupivacaine-induced central nervous system toxicity: a prospective, randomized animal study. J Anesth 30, 109–115 (2016). https://doi.org/10.1007/s00540-015-2069-x

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  • DOI: https://doi.org/10.1007/s00540-015-2069-x

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