利多卡因在静脉注射和蛛网膜下腔麻醉致死犬体内分布比较的研究

发布时间：2018-06-08 21:10

本文选题：利多卡因 + 静脉注射　；参考：《山西医科大学》2004年硕士论文

【摘要】：目的 (1) 建立犬的利多卡因静脉注射致死的动物模型，，验证员克明研究组建立的利多卡因蛛网膜下腔麻醉致死动物模型；观察和比较利多卡因静脉注射和蛛网膜下腔麻醉致死过程的生命体征和死后各组织脏器的病理变化；（2）建立组织脏器和体液中利多卡因的气相色谱和气相色谱-质谱联用分析检测方法；（3）比较利多卡因在静脉注射和蛛网膜下腔麻醉致死犬体内的分布，为利多卡因硬膜外麻醉意外死亡和中毒案件的法医学鉴定提供科学依据。方法（1）动物模型 ①利多卡因股静脉注射致死模型：犬9只，随机分为实验组（6只）和对照组（3只）两组，实验组犬5分钟内经股静脉匀速注入利多卡因5×15mg/kg，对照组犬注入等体积生理盐水。②利多卡因蛛网膜下腔麻醉致死模型：犬9只，随机分为实验组（6只）和对照组（3只）两组，实验组犬5分钟内蛛网膜下腔匀速注入利多卡因5×15mg/kg，对照组犬注入等体积生理盐水；（2）生命体征记录方法 BL-生物机能实验系统全程记录从开始给药到动物死亡的心电、血压和呼吸等主要生命体征的变化；（3）样品采集与处理心电、血压和呼吸全部消失时，迅速解剖动物， WP=5 取大脑、侧脑室脑脊液、背侧脑脊液、不同脊髓节段（颈髓、胸髓、腰髓、骶髓），心、肺、肝、脾、肾、胆汁、尿、心血、周围血、注射部位肌肉和注射部位20cm以外肌肉等组织脏器和体液，即刻检测实验组犬各脏器和体液中利多卡因含量，对照组犬各脏器和体液用作空白检材；（4）病理观察取大脑、小脑、脊髓、心、肺、肝、脾、肾，用4%甲醛固定，石蜡包埋，切片，HE染色，光镜观察；（5）检测利多卡因方法样品经酸、碱化处理后，乙醚萃取，气相色谱和气相色谱-质谱联用检测，根据利多卡因的特征离子峰、保留时间定性与内标法、工作曲线法定量。结果 ( 1 ) 症状静脉注射实验组动物开始给药后1~2min出现瞳孔缩小、呼吸困难、口吐粘稠状白色泡沫、失声、肌肉震颤、角弓反张、大小便失禁、对外界刺激极度敏感。蛛网膜下腔麻醉实验组动物在阻滞过程中四肢感觉缺失、强直；开始注药后1~2min开始出现肌肉震颤、角弓反张、大小便失禁。静脉注射和蛛网膜下腔麻醉对照组均未出现以上症状，未出现死亡。（2）生命体征静脉注射实验组犬的心电、血压和呼吸消失的平均时间分别为8±2.8 min、6.5±0.7 min、6.5±0.7min。蛛网膜下腔麻醉实验组犬的心电、血压和呼吸消失的平均时间分别为14.3±5.5 min、12.3±5.1 min、17±10.8min。（3）病理变化静脉注射实验组和蛛网膜下腔麻醉实验组犬的各组织脏器呈现明显的非特异的急死的征象。（4）利多卡因在犬体内的分布静脉注射实验组犬体内利多卡因的平均含量从高到低依次为：肾（1005.4±515.4μg/g）、心（398.3±377.9μg/g）、肺 WP=6 （320±270.5μg/g）、脾（197.6±113μg/g）、大脑（152.2±128.1μg/g）、肝（54.6±35.2μg/g）、周围血（50.3±52.9μg/ml）、胆汁（49.3±48.2μg/ml）、心血（48.3±37μg/ml）、颈段脊髓（30±28μg/g）、胸段脊髓（29.3±28.3μg/g）、注射部位肌肉（24.6±9.6μg/g）、腰段脊髓（22.6±19.7μg/g）、注射部位20cm以外的肌肉（21±9.8μg/g）、侧脑室脑脊液（12±14.14μg/ml）、尿（10μg/ml）、背侧脑脊液（8.77μg/ml）、骶段脊髓（8.25±0.29μg/g ）；肾、心、肺、脾、大脑、肝、周围血、胆汁、心血、颈段脊髓、胸段脊髓、注射部位肌肉、腰段脊髓、注射部位20cm以外的肌肉、侧脑室脑脊液、尿、背侧脑脊液、骶段脊髓与周围血中利多卡因含量之比分别为： 24.3±26.1、11.7±11.7、6.4±5.7、8.5±6.5、3.5±0.8、1.5±0.8、1.9±1.5、1.0±0.8、1.1±0.9、1±0.7、0.7±0.6、1.6±2.1、0.2±0.01、0.3±0.05、1±0.2、0.5±0.5。蛛网膜下腔麻醉实验组犬体内利多卡因的平均含量从高到低依次为：背侧脑脊液（1650.4±859.6μg/ml）、骶段脊髓（1216.6±1189.2μg/g）、胸段脊髓（1197.6±1019.4μg/g）、侧脑室脑脊液（1144.5±1656.8μg/ml）、腰段脊髓（1071.8±871.6μg/ g）、颈段脊髓（954.4±406.3μg/ g）、肺（220.3±233.1μg/ g）、肾（177±192.2μg/ g）、注射部位肌肉（153.6±150.9μg/ g）、心（109.6±88μg/ g）、大脑（91.8±77μg/ g）、脾（72.2±64.7μg/ g）、心血（37.1±27μg/ml）、肝（31.5±35.8μg/ g）、周围血（28±22μg/ml）、胆汁（13±9.4μg/ml）、注射部位20cm以外的肌肉（13±7.7μg/ g）、尿（11±5.6μg/ml）；背侧脑脊液、骶段脊髓、胸段脊髓、侧脑室脑脊液、腰段脊髓、颈段脊髓、肺、肾、注射部位肌肉、心、大脑、脾、心血、尿、胆汁、肝、注射部位20cm以外的肌肉与周围血中利多卡因含量之比分别为: 67±38.3、80.5±140.5、82.1±129.7、100.8±181.9、69.1±110.2、52.5±55.5、17.4±33.3、8.1±11、9.8±15.4、4.9±4.6、3.7±2、3.4±4.3、1.43±1、0.6±0.4、1.5±1.5、0.9±1.4。 WP=7 小结 1　本研究建立了利多卡因静脉注射致死的动物模型，验证了员克明研究组建立的利多卡因蛛网膜下腔麻醉致死的动物模型。利多卡因
[Abstract]:objective
(1) to establish an animal model of lidocaine intravenous lethal injection in canine, to verify the lethal animal model of lidocaine subarachnoid anaesthesia established by the Kmin research group, and to observe and compare the vital signs of lidocaine intravenous injection and subarachnoid anesthesia and the pathological changes of organs after death.
(2) establish a method for the determination of lidocaine in tissue viscera and body fluid by gas chromatography and gas chromatography-mass spectrometry.
(3) compare the distribution of lidocaine in intravenous and subarachnoid anaesthesia in dogs, and provide a scientific basis for forensic identification of cases of accidental death and poisoning of lidocaine epidural anesthesia.
Method
(1) animal model (1) lethal model of lidocaine femoral vein injection: 9 dogs were randomly divided into experimental group (6) and control group (3 rats). The experimental group was injected with lidocaine 5 * 15mg/kg through femoral vein in 5 minutes, and the control group was injected with equal volume of saline. (2) the death model of lidocara subarachnoid anesthesia: 9 dogs randomly. The experimental group was divided into the experimental group (6) and the control group (3 rats). The experimental group was injected with lidocaine 5 x 15mg/kg in the subarachnoid space in 5 minutes, and the control group was injected with equal volume of normal saline.
(2) the life sign recording method BL- biological function experiment system records the changes of major vital signs, such as the electrocardiogram (ECG), blood pressure and respiration, from the beginning to the death of the animal.
(3) when samples are collected and processed, ECG and blood pressure and respiration disappear, animals are dissected quickly.
WP=5
Cerebrum, lateral ventricle cerebrospinal fluid, dorsal cerebrospinal fluid, different spinal segment (cervical spinal cord, thoracic pulp, lumbar pulp, sacral pulp), heart, lung, liver, spleen, kidney, bile, urine, blood, peripheral blood, intramuscular injection site and 20cm muscle and body fluid outside the injection site, the content of lidocaine in the organs and body fluid of the experimental group and the control group of the dogs were immediately detected. The apparatus and body fluids are used as blank inspection materials.
(4) the brain, cerebellum, spinal cord, heart, lung, liver, spleen and kidney were fixed by 4% formaldehyde, paraffin embedded, sectioning, HE staining and light microscopy.
(5) detection of lidocaine method samples by acid, alkali treatment, ether extraction, gas chromatography and gas chromatography-mass spectrometry combined detection, according to the characteristic ion peak of lidocaine, retention time qualitative and internal standard method, the work curve method quantitative.
Result
(1) in the experimental group, the pupil of 1~2min in the experimental group was reduced, the respiratory difficulty, the puke and the sticky white foam, the sound loss, the muscle tremor, the angle arch, the incontinence, and the extreme sensitivity to the external stimuli. The animals in the subarachnoid anesthesia experiment group were feeling missing and ankylosis during the block of the block, and 1~2 after the drug injection. Min began to develop muscle tremor, armature reversal, fecal incontinence. Intravenous injection and subarachnoid anesthesia control group did not appear above symptoms, no deaths.
(2) the average time of dogs' ECG, blood pressure and respiration in the experimental group was 8 + 2.8 min, 6.5 + 0.7 min and 6.5 + 0.7min. subarachnoid anaesthesia in the experimental group. The average time of blood pressure and respiration disappeared was 14.3 + 5.5 min, 12.3 + 5.1 min, and 17 + 10.8min., respectively.
(3) pathological changes showed that the visceral organs of the experimental group and the subarachnoid anesthesia group showed obvious nonspecific signs of sudden death.
(4) the distribution of lidocaine in the canine experimental group, the average content of lidocaine in the dog was from high to low in the following order: kidney (1005.4 + 515.4 g/g), heart (398.3 + 377.9 mu g/g), lung
WP=6
(320 + 270.5 mu g/g), the spleen (197.6 + 113 mu g/g), the brain (152.2 + 128.1 u g/g), the liver (54.6 +. 35.2 u g/g), the peripheral blood (50.3 +. 52.9 mu), the bile (49.3 + 48.2 mu), the heart blood (48.3 + 152.2 g/ml), the cervical spinal cord (152.2), the thoracic spinal cord (+ + g/g), the lumbar spinal cord (+ = g/g), the injection site 20cm Muscle (21 + 9.8 g/g), lateral ventricle cerebrospinal fluid (12 + 14.14 mu g/ml), urine (10 mu g/ml), dorsal cerebrospinal fluid (8.77 g/ml), sacral spinal cord (8.25 + 0.29 u g/g), kidney, heart, lung, spleen, brain, liver, peripheral blood, bile, heart blood, cervical spinal cord, thoracic spinal cord, injection site muscle, lumbar spinal cord, muscle outside the injection site 20cm, lateral ventricle brain ridge The ratio of the content of lidocaine in liquid, urine, dorsal cerebrospinal fluid, sacral spinal cord and peripheral blood were 24.3 + 26.1,11.7 + 11.7,6.4 + 5.7,8.5 + 6.5,3.5 + 0.8,1.9 + 0.8,1.9 + 0.8,1.1 + 0.8,1.1 + 0.9,1 + 0.7,0.7 + 0.7,0.7 + + 0.7,0.7 +. The volume from high to low was: dorsal cerebrospinal fluid (1650.4 + 859.6 g/ml), sacral spinal cord (1216.6 + 1189.2, g/g), thoracic spinal cord (1197.6 + 1019.4 u g/g), lateral ventricle cerebrospinal fluid (1144.5 + 1656.8 u g/ml), lumbar spinal cord (1071.8 + 871.6 mu g/ g), cervical spinal cord (954.4 + 406.3 g/ g), lung (220.3 + 1197.6 g), kidney (g/ + g/ g), injection site Muscles (153.6 + 150.9 g/ g), the heart (109.6 + 88 g/ g), the brain (91.8 + 77 mu g), spleen (72.2 + 64.7 u g/ g), heart blood (37.1 + 27 u g/ml), liver (31.5 + 35.8 g/ g), peripheral blood (28 + trillion g/ml), bile (+ +), dorsal cerebrospinal fluid, sacral spinal cord, thoracic spinal cord, side The ratio of cerebral ventricle cerebrospinal fluid, lumbar spinal cord, cervical spinal cord, lung, kidney, injection site muscle, heart, brain, spleen, heart blood, urine, bile, liver, and injection site 20cm is 67 + 38.3,80.5 + 140.5,82.1 + 129.7100.8 + 181.9,69.1 + 110.2,52.5 + 110.2,52.5 + 33.3,8.1 + 110.2,52.5 + 15.4,4.9 + 4.6,3.7 + 2,3.4 + 4.3,1.43 + 1,0.6 + 0.4,1.5 + 1.5,0.9 + 1.4.
WP=7
Summary
1 this study established the animal model of lidocaine intravenous lethal injection, and verified the animal model of lidocaine subarachnoid anesthesia established by the member of the member kming research group. Lidocaine
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2004
【分类号】：D919

【引证文献】