咪达唑仑对局部麻醉药致惊厥神经毒性的影响

目的从致惊厥的行为学角度探讨咪达唑仑对局部麻醉药罗哌卡因、布比卡因、利多卡因及氯普鲁卡因致惊厥毒性的影响。方法 160只小鼠随机平行进入罗哌卡因、布比卡因、利多卡因和氯普鲁卡因4个实验。每个实验又随机分为咪达唑仑0(正常对照),0.25,0.5和1.0mg.kg-1组。各组小鼠先sc给予咪达唑仑20min后,再分别ip给予罗哌卡因85.9mg.kg-1,布比卡因48mg.kg-1,利多卡因80mg.kg-1或氯普鲁卡因250mg.kg-1,咪达唑仑0mg.kg-1对照组ip给予生理盐水;观察小鼠惊厥潜伏期、持续时间等;另外180只小鼠随机平行进入罗哌卡因、布比卡因、利多卡因和氯普鲁卡因4个实验。每个实验再随机分为咪达唑仑0(正常对照),0.5和1.0mg.kg-1组。按序贯法分析咪达唑仑对罗哌卡因、布比卡因、利多卡因及氯普鲁卡因致惊厥半数有效量(ED50)的影响。结果与正常对照组相比,咪达唑仑0.25,0.5和1mg.kg-1可延长局部麻醉药致小鼠惊厥潜伏期〔罗哌卡因:从162±21延长到186±50,352±229和(420±255)s;布比卡因:从136±19延长到227±40,485±355和(234±223)s(P<0.01);利多卡因:从164±34延长到247±101,216±54和(421±168)s;氯普鲁卡因:从183±63延长到238±131,392±219和(420±211)s〕;可缩短惊厥持续时间〔罗哌卡因:从914±306缩短到336±172,248±70和(290±42)s(P<0.01);布比卡因:从537±175缩短到442±129,131±147和(30±62)s;利多卡因:从26±9缩短到23±5,27±4和(16±5)s;氯普鲁卡因:从304±93缩短到269±184,123±145和(114±140)s〕;咪达唑仑0.5和1.0mg.kg-1可增加局部麻醉药致惊厥的ED50〔罗哌卡因:从51.2增加到68.1和89.3mg.kg-1;布比卡因:从38.6增加到50.3和57.2mg.kg-1;利多卡因:从48.8增加到71.5和86.2mg.kg-1;氯普鲁卡因:从152.5增加到254.1和190.6mg.kg-1(P<0.01)〕。结论咪达唑仑可拮抗局部麻醉药的致惊厥作用,降低其中枢神经系统毒性。

Effect of midazolam on local anesthetics-induced convulsion

OBJECTIVE To observe the effect of midazolam on local anesthetics-induced convulsion. METHODS One hundred-sixty mice were ramdomly divided into ropivacaine, bupivacaine, lidocaine and chloroprocaine experiments, each of which was then divided into midazdam 0(normal control), 0.25, 0.5 and 1.0 mg·kg^-1 groups. Mice were ip given midazdam and 20 min later sc given ropivacaine 86 mg·kg^-1, bupivacaine 48 mg·kg^-1, lidocaine 80 mg·kg^-1 and chloroprocaine 250 mg·kg^-1, respectively. The convulsion latency and convulsion duration were observed. Another 180 mice were randomly divided into 4 experiments, which were again divided into midazolam 0(normal control), 0.5 and 1.0 mg·kg^-1 groups. The ED₅₀ was analyzed by sequential method in mice. RESULTSCompared with normal control group, the convulsion latency of local anesthetics induced convulsion was extended by midazolam 0.25, 0.5 and 1 mg·kg^-1〔for ropivacaine, from 162±21 to 186±50，352±229 and (420±255)s；for bupivacaine, from 136±19 to 227±40，485±355 and (234±223)s(P<0.01); for lidocaine, from 164±34 to 247±101，216±54 and (421±168)s; for chloroprocaine, from 183±63 to 238±131，392±219 and (420±211)s〕. The convulsion duration was shortened 〔for ropivacaine, from 914±306 to 336±172，248±70 and (290±42)s(P<0.01), for bupivacaine, from 537±175 to 442±129，131±147 and (30±62)s，for lidocaine, from 26±9 to 23±5，27±4 and (16±5)s，for chloroprocaine, from 304±93 to 269±184，123±145 and (114±140)s〕. The ED₅₀ was improved by midazolam 0.5 and 1.0 mg·kg^-1〔for ropivacaine, from 51.2 to 68.1 and 89.3 mg·kg^-1, for bupivacaine, from 38.6 to 50.3 and 57.2 mg·kg^-1; for lidocaine, from 48.80 to 71.5 and 86.2 mg·kg^-1 and for chloroprocaine, from 152.5 to 254.1 and 190.6 mg·kg^-1(P<0.01)〕. CONCLUSION Midazolam can antagonize local anesthetics-induced convulsion and prevent neurotoxicity of local anesthetics.