不同剂量右美托咪定预注对利多卡因神经毒性的影响

目的 比较不同剂量右美托咪定(dexmedetomidine,Dex)预注对利多卡因致白兔中枢神经毒性的影响及可能机制. 方法 将40只新西兰白兔按随机数字表法分为4组(A、B、C、D组),每组10只:A组通过颈内静脉泵入含Dex 10 μg/kg的生理盐水8 ml,10 min后以4 mg· kg-1· min-1泵入利多卡因直到出现惊厥;B组泵入含Dex 5 μg/kg的生理盐水8 ml,同法泵入利多卡因;C组泵入等量生理盐水,同法泵入利多卡因;D组只泵入生理盐水8 ml.于白兔惊厥时抽血测利多卡因浓度,记录利多卡因剂量及发生惊厥时间,测脑组织天冬氨酸(aspartate,Asp)、谷氨酸(glutamic acid,Glu)、甘氨酸(glycine,Gly)、γ-氨基丁酸(γ-aminobutyric acid,GABA)的含量. 结果 产生中枢神经毒性所需利多卡因剂量、利多卡因血药浓度及发生惊厥时间,A组分别为:(240±48) mg,(6.4±0.8)μg/kg,(822±122)s]、B组分别为:(230±51) mg,(6.3±0.5)μg/kg,(802±114)s]较C组分别为:(137±37) mg,(5.4±0.6) μg/kg,(510±76)s]明显增加,差异有统计学意义(P＜0.05);Asp、Glu、Gly、GABA的含量,A组分别为:(3.5±1.0)、(4.0±1.9)、(10.1±1.9)、(16.5±2.2) μmol/g]、B组分别为:(3.7±0.8)、(4.2±1.9)、(11.4±2.2)、(17.4±2.4) mol/g]、C组分别为:(4.7±1.0)、(6.8±1.9)、(13.7±1.9)、(20.9±3.4) μmol/g]明显高于D组分别为:(1.5±0.8)、(2.4±1.2)、(4.7±1.6)、(5.7±2.8) μmol/g],差异有统计学意义(P＜0.05),而C组又明显高于A、B组(P＜0.05). 结论 预注Dex可以延缓利多卡因致惊厥反应的发生,增加利多卡因神经毒性的阈值,对中枢神经有一定的保护作用.

Effects and possible mechanism of different doses dexmedetomidine pretreatment on lidocaine toxicity to nervus centralis of albino rabbit

Objective To investigate the effects and possible mechanism of different doses dexmedetomidine (Dex) pretreatment on lidocaine toxicity to nervus centralis of albino rabbit.Methods Forty New-Zealand albino rabbit were randomly divided into 4 groups (n=10).Group A and B were received infusion of 8 ml mixture Dex (respectively,5 μg/kg and 10 μg/kg) and saline,10 min later lidocaine was pumped at the rate of 4 mg·kg-1 ·min-1 until occurrence of hyperspasmia.The equal dosis of saline and lidocaine were given in group C,but group D were only received saline.The hematoplasma density of lidocaine was measure when hyperspasmia occurred,the doses of lidocaine,the appearing times of lidocaine-induced hyperspasmia were observed,the concentration of aspar tate,glutamic acid,glycine and γ-aminobutyric acid in brain architecture were recorded.Results Compared with group C (137±37) mg,(5.4±0.6) μg/kg,(510±76) s,respectively],the doses of lidocaine when neurotoxicity occur,the plasmic density of lidocaine and the appearing times of lidocaine-induced hyperspasmia were all increased obviously in group A (240±48) mg,(6.4±0.8) μg/kg,(822±122) s,respectively] and B (230±51) mg,(6.3±0.5) μg/kg,(802±114) s,respectively] (P＜0.05).Compared with group D (1.5±0.8),(2.4±1.2),(4.7±1.6),(5.7±2.8) μ.mol/g,respectively],the concentration of aspartate,glutamic acid,glycine and gamma-aminobutyric acid in brain architecture were all increased in group A (3.5±1.0),(4.0± 1.9),(10.1±1.9),(16.5±2.2) μmol/g,respectively],B(3.7±0.8),(4.2±1.9),(11.4±2.2),(17.4±2.4) μmol/g,respectively] and C(4.7±1.0),(6.8±1.9),(13.7±1.9),(20.9±3.4) μmol/g,respectively](P＜0.05),then in group C obviously higher than in group A and B (P＜0.05).Conclusions Dex pretreatment may postpone the occurrence of lidocaine-induced hyperspasmia and raise the neurotoxic threshold of lidocaine,so it has protection on nervus centralis.