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不同浓度利多卡因和罗哌卡因混合液对大鼠中枢神经系统及心血管毒性的影响。

Effects of mixture of lidocaine and ropivacaine at different concentrations on the central nervous system and cardiovascular toxicity in rats.

机构信息

Department of Anesthesiology, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, China.

出版信息

Chin Med J (Engl). 2010 Jan 5;123(1):79-83.

PMID:20137580
Abstract

BACKGROUND

Lidocaine and ropivacaine are often combined in clinical practice to obtain a rapid onset and a prolonged duration of action. However, the systemic toxicity of their mixture at different concentrations is unclear. This study aimed to compare the systemic toxicity of the mixture of ropivacaine and lidocaine at different concentrations when administered intravenously in rats.

METHODS

Forty-eight male Wistar rats were randomly divided into 4 groups (n = 12 each): 0.5% ropivacaine (group I); 1.0% ropivacaine and 1.0% lidocaine mixture (group II); 1.0% ropivacaine and 2.0% lidocaine mixture (group III); and 1.0% lidocaine (group IV). Local anesthetics were infused at a constant rate until cardiac arrest. Electrocardiogram, electroencephalogram and arterial blood pressure were continuously monitored. The onset of toxic manifestations (seizure, dysrhythmia, and cardiac arrest) was recorded, and then the doses of local anesthetics were calculated. Arterial blood samples were drawn for the determination of local anesthetics concentrations by high-performance liquid chromatography.

RESULTS

The onset of dysrhythmia was later significantly in group IV than in group I, group II, and group III (P < 0.01), but there was no significant difference in these groups (P > 0.05). The onset of seizure, cardiac arrest in group I ((9.2 + or - 1.0) min, (37.0 + or - 3.0) min) was similar to that in group II ((9.1 + or - 0.9) min, (35.0 + or - 4.0) min) (P > 0.05), but both were later in group III ((7.5 + or - 0.7) min, (28.0 + or - 3.0) min) (P < 0.05). The onset of each toxic manifestation was significantly later in group IV than in group I (P < 0.01). The plasma concentrations of the lidocaine-alone group at the onset of dysrhythmia (DYS), cardiac arrest (CA) ((41.2 + or - 6.8) min, (59.0 + or - 9.0) min) were higher than those of the ropivacaine alone group ((20.5 + or - 3.8) min, (38.0 + or - 8.0) min) (P < 0.05). The plasma concentrations of ropivacaine inducing toxic manifestation were not significantly different among groups I, II, and III (P > 0.05).

CONCLUSIONS

The systemic toxicity of the mixture of 1.0% ropivacaine and 2.0% lidocaine is the greatest while that of 1.0% lidocaine is the least. However, the systemic toxicity of the mixture of 1.0% ropivacaine and 1.0% lidocaine is similar to that of 0.5% ropivacaine alone.

摘要

背景

在临床实践中,常将利多卡因和罗哌卡因联合使用,以达到起效迅速和作用时间延长的效果。然而,其不同浓度混合物的全身毒性尚不清楚。本研究旨在比较不同浓度的罗哌卡因和利多卡因混合物静脉注射时在大鼠体内的全身毒性。

方法

48 只雄性 Wistar 大鼠随机分为 4 组(n = 12):0.5%罗哌卡因(组 I);1.0%罗哌卡因和 1.0%利多卡因混合物(组 II);1.0%罗哌卡因和 2.0%利多卡因混合物(组 III);和 1.0%利多卡因(组 IV)。局部麻醉药以恒定速度输注,直至心脏骤停。连续监测心电图、脑电图和动脉血压。记录毒性表现(抽搐、心律失常和心脏骤停)的发作,并计算局部麻醉药的剂量。通过高效液相色谱法测定动脉血样中的局部麻醉药浓度。

结果

与组 I、组 II 和组 III 相比,组 IV 心律失常的发作明显延迟(P < 0.01),但这些组之间无显著差异(P > 0.05)。组 I 中抽搐、心脏骤停的发作时间为(9.2 ± 1.0)min、(37.0 ± 3.0)min,与组 II 相似(9.1 ± 0.9)min、(35.0 ± 4.0)min(P > 0.05),但均晚于组 III(7.5 ± 0.7)min、(28.0 ± 3.0)min(P < 0.05)。与组 I 相比,组 IV 中每种毒性表现的发作均明显延迟(P < 0.01)。组 IV 中心律失常(DYS)、心脏骤停(CA)发作时的利多卡因血浆浓度(41.2 ± 6.8)min、(59.0 ± 9.0)min 高于组 I 中单独使用利多卡因的浓度(20.5 ± 3.8)min、(38.0 ± 8.0)min(P < 0.05)。组 I、组 II 和组 III 中引起毒性表现的罗哌卡因血浆浓度无显著差异(P > 0.05)。

结论

1.0%罗哌卡因和 2.0%利多卡因混合物的全身毒性最大,而 1.0%利多卡因的全身毒性最小。然而,1.0%罗哌卡因和 1.0%利多卡因混合物的全身毒性与 0.5%罗哌卡因单独使用相似。

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