【作者】 张潮；

【导师】 贠克明；

【作者基本信息】 山西医科大学 ， 法医学， 2007， 硕士

【摘要】 目的(1)建立犬的利多卡因硬膜外麻醉死后弥散模型;(2)研究利多卡因在犬体内死后弥散的特点和规律;(3)比较处死方式和给药时间对利多卡因弥散的影响,探讨死后弥散的影响因素;(4)为利多卡因硬膜外麻醉意外致死案件的法医学鉴定提供科学依据。方法1.动物模型1.1空气栓塞处死犬死后弥散模型犬30只,随机分为处死后即刻给药组(18只)和处死后不同时间给药组(12只)。处死后即刻给药组:于生命体征消失后,立刻匀速注入一倍极量盐酸利多卡因(13mg/kg,按犬、人体型系数推算),5min内注完,置于室温下(17～21℃),按3样品采集方法在给药后0、12、24、48、72、96小时解剖动物取材。处死后不同时间给药组:于生命体征消失后0、1、3、6、12小时匀速注入一倍极量盐酸利多卡因(13mg/kg,按犬、人体型系数推算),5min内注完,置于室温下(17～21℃),按3样品采集方法在给药后即刻解剖动物取材。1.2二氧化碳处死犬死后弥散模型犬18只,于生命体征消失后,立刻匀速注入一倍极量盐酸利多卡因(13mg/kg,按犬、人体型系数推算),5min内注完,置于室温下(17～21℃),按3样品采集方法在给药后0、12、24、48、72、96小时解剖动物取材。2.生命体征记录方法用BL-生物机能实验系统(成都泰盟有限公司),全程记录实验犬死亡过程中的心电、血压和呼吸等生命体征的变化。3.样品的采集与处理硬膜外给药后,置于室温下(17～21℃),不同时间点解剖动物,采集脑、不同脊髓节段(颈段脊髓、胸段脊髓、腰段脊髓、骶段脊髓)、心、肺、肝、脾、肾、胆汁、尿、右心室血、左心室血、上腔静脉血、下腔静脉血、玻璃体液、注射部位肌肉和颞肌(对照肌肉)等组织脏器和体液,即刻检测,每只犬的检材在48小时内检测完毕。检测样品经酸、碱化处理后,乙醚萃取,根据保留时间和特征离子峰气相色谱-质谱联用定性,内标法、工作曲线法气相色谱-质谱联用定量。结果1.利多卡因在空气栓塞致死犬体内的死后弥散(1)处死后即刻给药组的实验显示:利多卡因在注入机体的即刻就由硬膜外弥散入脊髓、脑和椎管内外静脉丛,并且由椎管内外静脉丛迅速进入上下腔静脉、心血和肺组织。左心室血中利多卡因含量变化明显,由开始的4.7±3.8μg/ml上升到72小时解剖时的21.0±9.4μg/ml,而肺中利多卡因的含量在24小时后有所下降,提示肺组织在给药后的早期可能成为利多卡因的一个蓄积库,左心室血中利多卡因含量的增高可能为肺中利多卡因随着死亡时间的延长逐渐弥散入左心血液中引起的。给药12小时后,心、肝、肾、注射部位肌肉和尿液均受到利多卡因死后弥散的影响。脾、颞肌、胆汁、玻璃体液不受死后弥散的影响,此特点可区别生前给药还是死后给药。(2)处死后不同时间给药组的实验显示:分别在0、1、3、6、12小时给药即刻解剖时,利多卡因在各组织脏器和血液中的含量变化无统计学差异,说明死后不同时间给药不会对利多卡因的死后弥散造成影响。2.利多卡因在二氧化碳致死犬体内死后弥散的实验显示:除了脑和各脊髓段在各时间点均检出利多卡因外,在其它组织中,仅于给药后48、72、96小时在下腔静脉血中检出利多卡因,利多卡因的弥散很局限,说明二氧化碳处死方式对利多卡因的死后弥散影响较大。小结1本文建立了利多卡因硬膜外麻醉意外的死后弥散动物模型,结果显示:利多卡因可发生死后弥散,所建模型可应用于硬膜外麻醉意外死亡和中毒案件的法医学研究。2利多卡因在空气栓塞致死犬体内的死后弥散表明:由硬膜外给药后利多卡因在数分钟内迅速分布于上下腔静脉血、心血和肺组织中,这与利多卡因本身的理化性质和给药途径有很大关系。肺组织在给药后的早期可能成为利多卡因的一个蓄积库,随着死亡时间的延长逐渐的影响到心血中利多卡因含量。脾、颞肌、胆汁和玻璃体液不受死后弥散的影响,此特点可区别生前给药还是死后给药。3利多卡因在死后不同时间给药犬体内的死后弥散表明:在死后的一段时间内,机体的内环境(如:pH值变化、腐败的产生等)还没有发生大的变化之前,给药时间不会对利多卡因的死后弥散造成影响。4利多卡因在二氧化碳致死犬体内的死后弥散表明:二氧化碳窒息处死方法可对利多卡因的死后弥散造成很大影响。提示在建立死后弥散模型时,应该注意到处死方式对毒物在体内死后弥散造成的影响。5在进行硬膜外麻醉意外死亡和中毒案件的法医学鉴定中,应综合考虑死后不同时间对体内利多卡因含量的影响;利多卡因的死后弥散与其理化特性、在体内的电离状态和弥散距离有关系;随着腐败的发生,生物屏障的破坏使其通透性增加也可能会促进盐酸利多卡因的弥散。在疑为利多卡因麻醉致死案件取材时,要考虑死后弥散对检材中利多卡因含量造成的影响,心血和周围血的提取应防止相互污染,先结扎采血部位主要脉管系统通路,防止取材时血液流动造成的影响。更多还原

【Abstract】 Objective:1.To develop a postmortem diffusion model of lidocaine in dogs after an epidural administration.2.To investigate the postmortem diffusion of lidocaine in dogs.3.To compare postmortem diffusion of lidocaine in dogs with different way of executes and administration times.4.To provide a scientific evidence for the forensic identification of the anesthesia accident caused by lidocaine.Methods:1.Animal models:1.1 Group executed by an aeroembolism:30dogs were executed by an aeroembolism.When the vital signs of dogs disappeared,18dogs were given an epidural anesthesia at an even speed in five minutes with 13mg/kg weight of lidocaine hydrochloride,then sampled in 0,12,24,48,72,96 hours after the administration(n=3 per time-point).The other 12dogs were given an epidural anesthesia with an even speed in five minutes with 13mg/kg weight of lidocaine hydrochloride respectively at 1,3,6,12hours after the vital signs of dogs had disappeared(n=3 per time-point),then collected samples at once.1.2 Group executed by carbon dioxide(18dogs):18dogs were given an epidural anesthesia with an even speed in five minutes with 13mg/kg weight of lidocaine hydrochloride,then respectively collected samples in 0,12,24,48,72,96 hours after administration(n=3 per time-point).2.Record of vital signs:By a biological function system,the vital signs such as electro cardia,blood pressure and respiration from beginning of the execute to the death of dogs were recorded.3.Collection of samples:After administration,the dogs were placed at room temperature(17～21℃),the brain,spinal cord(cervical spinal cord,thoracic spinal cord,lumbar spinal cord,sacrum spinal cord),heart,lung,liver,spleen,kidney,bile,urine,humor vitreous,blood of right ventricle,blood of left ventricle,blood of superior vena,blood of inferior vena,muscle in injection location and temporalis(muscle in no injection location)-were collected and detected immediately.4.Analysis:The samples were extracted with ether.Analysis was performed by a GC equipped with a NPD and a GC-MS.The qualitative analysis was based on retention time in the chromatographic system coupled with the ion fragmentation spectrum in the mass spectrometer. The quantitative analysis was based on an internal standard method.Results:1.Group of executed by aeroembolism:The series of administration when the vital signs of dogs disappeared:In dogs dissected immediately,lidocaine were detected in blood of inferior vena,blood of superior vena,blood of right ventricle,blood of left ventricle and lung.The concentrations of lidocaine in blood of left ventricle were changed obviously,increased from 4.7±3.8gg/ml to 21.0±9.4μg/ml in 72 hours.The concentrations in lung,there was a little decreasing after 24 hours,It indicated that the lidocaine concentrations increased in blood of left ventricle may ascribe to the diffusion from lung.Heart,liver,kidney,urine and muscle in injection location were all affected by the postmortem diffusion.Spleen,tempotal muscle,bile and humor vitreous had not been affected by the postmortem diffusion.The series of administration at 1,3,6,12 hours after the vital signs of dogs disappeared:The postmortem diffusion were similar with dogs administration when the vital signs of dogs disappeared.2. Group of executed by carbon dioxide:Lidocaine were detected in blood of inferior vena at 48,72, 96 hours after administration,It indicated that the postmortem diffusion of lidocaine should be influenced by the method of sacrifice.Conclusion:1.The study has established the postmortem diffusion models of epidural administration with lidocaine,It can be applied to the forensic identification of the epidural anesthesia accident.2.The results of lidocaine sacrificed by aeroembolism showed that,lidocaine detected in heart blood,lung and blood in inferior caval vein in a few minutes after epidural anesthesia,which was related to the physico-chemical property of lidocaine and the path of administration.Lung may be another reservoir in the early stage after death,then with the time lasting,the concentration of lidocaine in heart blood were effected.There was no postmortem diffusion in spleen,tempotal muscle,bile and humor vitreous.Whether lidocaine was detected in the matrix could be regarded as the evidence for the poisoning or postmortem intragastric administration.3.The postmortem diffusion of lidocaine in different time administration groups showed that,it had not significant effect on the postmortem diffusion in the early stage after death.4.The group of sacrificed by carbon dioxide showed that,the cause of death would take an effect on the postmortem diffusion of lidocaine.5.It is important to consider the phenomenon of postmortem diffusion.in the forensic identification of epidural anesthesia accident case.The postmortem diffusion of lidocaine was related to the physico-chemical property of lidocaine,the rate of electro-ionization and the distance to reservoir.With the development of gangrenous, destruction of biological barrier can also facilitate the diffusion of lidocaine hydrochloride.The blood in heart and periph should be discriminated,for lest to pollute each other.更多还原