中华医学杂志
中華醫學雜誌
중화의학잡지
National Medical Journal of China
2012年
33期
2362-2365
,共4页
罗哌卡因%药物毒性%脂肪乳%丙泊酚%半数致死量
囉哌卡因%藥物毒性%脂肪乳%丙泊酚%半數緻死量
라고잡인%약물독성%지방유%병박분%반수치사량
Ropivacaine%Drug toxicity%Lipid%Propofol%LD50
目的 探讨脂肪乳预先给药对罗哌卡因致大鼠神经毒性及半数致死剂量的影响,并与传统抗惊厥药咪达唑仑及丙泊酚相比较.方法 (1)将120只(雌雄各半)SD大鼠按性别以数字随机法分为4组,即对照组(C),脂肪乳组(L),咪达唑仑组(M)和丙泊酚组(P).在腹腔注射罗哌卡因前,对照组先静脉缓推10 ml/kg生理盐水;L组先静脉缓推脂肪乳10 ml/kg;M组先静脉缓推生理盐水,剂量为10 ml/kg×体质量-应注射咪达唑仑体积,再注射咪达唑仑0.23 mg/kg;P组先静脉缓推生理盐水,剂量为10 ml/kg×体质量-应注射丙泊酚体积,再注射丙泊酚4 ml/kg,然后各组再于腹腔注射罗哌卡因44 mg/kg.以出现肢体抽搐为惊厥标准.观察其致惊厥率.并于大鼠惊厥发作时采集血液测血罗哌卡因浓度,记录从给药完毕到惊厥发作时间.(2)将100只SD雄鼠编号,用序贯法测4组罗哌卡因LD50.根据预实验结果选择各组罗哌卡因的剂量范围,按等比例0.85分为6个剂量亚组,各组预先给药方法和剂量同(1).结果 对照组惊厥率为43.3％,LD50(C)=64.39 mg/kg,致惊厥时平均血罗哌卡因浓度为(1.65±0.30) μg/kg;脂肪乳组惊厥率为70.0％,LD50(L) =55.45mg/kg,平均血药浓度为(3.45±0.26)μg/kg;咪达唑仑组惊厥率为0％,LD50(M)=88.40 mg/kg;丙泊酚惊厥率组为13.3％,LD50(P) =90.20 mg/kg,平均血药浓度为1.73 ±0.14 μg/kg.与对照组比,脂肪乳组惊厥率升高,半数致死量降低,两组间差异有统计学意义(P＜0.05).咪达唑仑组与丙泊酚组惊厥率降低,LD50升高,与对照组相比差异有统计学意义(P＜0.05).脂肪乳组的血药浓度最高,与对照组比差异有统计学意义(P ＜0.001).丙泊酚组血药浓度与对照组之间差异无统计学意义(P =0.895).各组大鼠出现惊厥时间差异无统计学意义(P＞0.05).结论 咪达唑仑与丙泊酚有神经毒性预防作用,并能提高罗哌卡因半数致死剂量.脂肪乳加重了罗哌卡因神经毒性并且降低其半数致死剂量.预先给予脂肪乳预防局部麻醉药物中毒反应有潜在风险.
目的 探討脂肪乳預先給藥對囉哌卡因緻大鼠神經毒性及半數緻死劑量的影響,併與傳統抗驚厥藥咪達唑崙及丙泊酚相比較.方法 (1)將120隻(雌雄各半)SD大鼠按性彆以數字隨機法分為4組,即對照組(C),脂肪乳組(L),咪達唑崙組(M)和丙泊酚組(P).在腹腔註射囉哌卡因前,對照組先靜脈緩推10 ml/kg生理鹽水;L組先靜脈緩推脂肪乳10 ml/kg;M組先靜脈緩推生理鹽水,劑量為10 ml/kg×體質量-應註射咪達唑崙體積,再註射咪達唑崙0.23 mg/kg;P組先靜脈緩推生理鹽水,劑量為10 ml/kg×體質量-應註射丙泊酚體積,再註射丙泊酚4 ml/kg,然後各組再于腹腔註射囉哌卡因44 mg/kg.以齣現肢體抽搐為驚厥標準.觀察其緻驚厥率.併于大鼠驚厥髮作時採集血液測血囉哌卡因濃度,記錄從給藥完畢到驚厥髮作時間.(2)將100隻SD雄鼠編號,用序貫法測4組囉哌卡因LD50.根據預實驗結果選擇各組囉哌卡因的劑量範圍,按等比例0.85分為6箇劑量亞組,各組預先給藥方法和劑量同(1).結果 對照組驚厥率為43.3％,LD50(C)=64.39 mg/kg,緻驚厥時平均血囉哌卡因濃度為(1.65±0.30) μg/kg;脂肪乳組驚厥率為70.0％,LD50(L) =55.45mg/kg,平均血藥濃度為(3.45±0.26)μg/kg;咪達唑崙組驚厥率為0％,LD50(M)=88.40 mg/kg;丙泊酚驚厥率組為13.3％,LD50(P) =90.20 mg/kg,平均血藥濃度為1.73 ±0.14 μg/kg.與對照組比,脂肪乳組驚厥率升高,半數緻死量降低,兩組間差異有統計學意義(P＜0.05).咪達唑崙組與丙泊酚組驚厥率降低,LD50升高,與對照組相比差異有統計學意義(P＜0.05).脂肪乳組的血藥濃度最高,與對照組比差異有統計學意義(P ＜0.001).丙泊酚組血藥濃度與對照組之間差異無統計學意義(P =0.895).各組大鼠齣現驚厥時間差異無統計學意義(P＞0.05).結論 咪達唑崙與丙泊酚有神經毒性預防作用,併能提高囉哌卡因半數緻死劑量.脂肪乳加重瞭囉哌卡因神經毒性併且降低其半數緻死劑量.預先給予脂肪乳預防跼部痳醉藥物中毒反應有潛在風險.
목적 탐토지방유예선급약대라고잡인치대서신경독성급반수치사제량적영향,병여전통항량궐약미체서륜급병박분상비교.방법 (1)장120지(자웅각반)SD대서안성별이수자수궤법분위4조,즉대조조(C),지방유조(L),미체서륜조(M)화병박분조(P).재복강주사라고잡인전,대조조선정맥완추10 ml/kg생리염수;L조선정맥완추지방유10 ml/kg;M조선정맥완추생리염수,제량위10 ml/kg×체질량-응주사미체서륜체적,재주사미체서륜0.23 mg/kg;P조선정맥완추생리염수,제량위10 ml/kg×체질량-응주사병박분체적,재주사병박분4 ml/kg,연후각조재우복강주사라고잡인44 mg/kg.이출현지체추휵위량궐표준.관찰기치량궐솔.병우대서량궐발작시채집혈액측혈라고잡인농도,기록종급약완필도량궐발작시간.(2)장100지SD웅서편호,용서관법측4조라고잡인LD50.근거예실험결과선택각조라고잡인적제량범위,안등비례0.85분위6개제량아조,각조예선급약방법화제량동(1).결과 대조조량궐솔위43.3％,LD50(C)=64.39 mg/kg,치량궐시평균혈라고잡인농도위(1.65±0.30) μg/kg;지방유조량궐솔위70.0％,LD50(L) =55.45mg/kg,평균혈약농도위(3.45±0.26)μg/kg;미체서륜조량궐솔위0％,LD50(M)=88.40 mg/kg;병박분량궐솔조위13.3％,LD50(P) =90.20 mg/kg,평균혈약농도위1.73 ±0.14 μg/kg.여대조조비,지방유조량궐솔승고,반수치사량강저,량조간차이유통계학의의(P＜0.05).미체서륜조여병박분조량궐솔강저,LD50승고,여대조조상비차이유통계학의의(P＜0.05).지방유조적혈약농도최고,여대조조비차이유통계학의의(P ＜0.001).병박분조혈약농도여대조조지간차이무통계학의의(P =0.895).각조대서출현량궐시간차이무통계학의의(P＞0.05).결론 미체서륜여병박분유신경독성예방작용,병능제고라고잡인반수치사제량.지방유가중료라고잡인신경독성병차강저기반수치사제량.예선급여지방유예방국부마취약물중독반응유잠재풍험.
Objective To assess the effects of lipid on ropivacaine-induced convulsion and LD50 in rats and compare with those of the traditional anticonvulsants midazolam and propofol.Methods Protocol 1:A total of 120 SD rats (60 males,60 females),weighing 200-300 g,were randomly assigned into 4 groups with equal males and females:lipid (L),midazolam (M) and propofol (P) and control (C).Rats were pretreated with 10 ml/kg lipid intravenously in group L,saline and 0.23 mg/kg madazolam (10 ml/kg in volume) sequentially in group M,saline and 4 mg/kg propofol (10 ml/kg in volume) in group P and saline 10 ml/kg in group C.Then ropivacaine 44 mg/kg (0.75％) was injected intraperitoneally into each rat.The convulsion rate in each group and the time of convulsion after ropivacaine injection were observed.Meanwhile,the plasma concentration of ropivacaine at the time of convulsion was measured.Protocol 2:Additional 100 male SD rats were used for the measurements of ropivacaine LDS0 with different pretreatments including lipid,midozolam,propofol and saline through the up-and-down method.Rats were randomly assigned into 4 groups similarly as protocol 1.The doses of ropivacaine in each group were determined according to our pilot study and 6 dosage levels with the same interval ratio 8.5 was applied in each group.The doses of these pretreatment drugs and administration methods were similarly as protocol 1.Results The convulsion rate after 44 mg/kg ropivaeaine ip injection was 43.3％ in group C,0％ in group M,13.3％ in group P and 70％ in group L.Lipid increased the convulsion rate significantly.The plasma concentration of ropivacaine at the time of convulsion was 1.65 ±0.30 μg/kg in group C,1.73 ±0.14 μg/kg in group P and 3.45±0.26 μg/kg in group L.The LD50 of ropivacaine in group C was 64.39 mg/kg,88.40 mg/kg in group M and 90.20 mg/kg in group P and 55.45 mg/kg in group L.Conclusions Midazolam and propofol not only decrease the convulsion rate of ropivacaine,but also increase its LD50.Lipid not only increases the convulsion rate of ropivacaine,but also decreases its LD50.The application of lipid for the prevention of local anesthetic toxicity has potential risks.
