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乌司他丁对亲体肝移植患儿脑损伤的影响

发布时间:2018-05-24 00:34

  本文选题:乌司他丁 + 肝移植 ; 参考:《天津医科大学》2017年硕士论文


【摘要】:目的:观察乌司他丁对亲体肝移植患儿脑损伤的影响及机制研究。方法:择期因先天性胆道闭锁行亲体肝移植术患儿60例为研究对象,年龄6~10月龄,体重6.5~9.5kg,ASA分级II或III级,肝功能Child-Pugh分级B~C级,供者平均年龄为33岁(22-50岁),供、受者血型相合,所有患儿全部采用静吸复合全身麻醉,手术方法均采取背驮式肝移植,切取供肝左外叶用于肝移植。按照随机数字表法,随机分为两组(n=30):对照组(C组)和乌司他丁组(U组)。麻醉诱导后至术毕,乌司他丁组静脉输注乌司他丁10000U/kg,对照组输注等剂量0.9%氯化钠注射液。于麻醉诱导后(T1)、无肝期30分钟(T2)、新肝期3小时(T3)及新肝期24小时(T4)采集中心静脉血样,采用ELISA法检测患儿血清中S-100β蛋白和神经元特异性烯醇化酶(NSE)浓度,采用放射免疫技术测定患儿血清中白介素-6(IL-6)、白介素-10(IL-10)及白介素-18(IL-18)的浓度,各时点记录心率、平均动脉压、中心静脉压和BIS值,采用儿童苏醒期谵妄评分量表(Pediatric Anesthesia Emergence Delirium,PAED)和贝利婴幼儿发展量表(BSID-Ⅱ),由经过培训的医师于手术前1天,术后第2周对患儿进行神经系统评分,评价患儿术后苏醒情况和患儿智力及运动发展情况,从而得知神经系统情况。结果:2组患儿年龄、手术时身体重量、手术持续时间、麻醉持续时间、无肝期、输液量和尿量比较,差异无统计学意义(P0.05)。2组T1时S-100β浓度和NSE浓度比较差异无统计学意义(P0.05)。与T1时比较,2组T2,3时S-100β浓度和NSE浓度升高(P0.05),T4时S-100β浓度和NSE浓度比较差异无统计学意义(P0.05),与对照组比较,乌司他丁组T2-4时血清S-100β蛋白和NSE浓度降低(P0.05),差异具有统计学意义。2组T1时血清IL-6、IL-10及IL-18浓度比较差异无统计学意义(P0.05)。与对照组比较,乌司他丁组T2-4时血清IL-6、IL-18浓度降低,血清IL-10浓度升高(P0.05),差异具有统计学意义,与患儿术前1d比较,两组患儿术后2周智力及运动发展指数均降低,与C组比较,患儿运动发展指数(Psychomotor Development Index,PDI)比较无统计学意义(P0.05),智力发展指数(Mental Development Index,MDI)下降较少(P0.05),PAED评分降低(P0.05),苏醒期谵妄评分降低,具有统计学意义。结论:亲体肝移植手术围术期存在脑损伤,于新肝期损伤最为严重,术后逐渐回落至基础水平,血清S-100β浓度和NSE水平升高与脑损伤呈正相关,可作为判断脑损伤的可靠指标,研究结果表明,与术前比较,2组患儿在T2和T3时血清S-100β蛋白和NSE水平升高,提示亲体部分肝移植术患儿围术期发生了脑损伤,其炎性反应是肝脏缺血再灌注诱发脑损伤的主要病理生理机制。本研究结果表明,给予乌司他丁后,患儿T2,3时血清S-100β蛋白和NSE水平、IL-6和IL-18浓度降低,血清IL-10浓度升高,乌司他丁能在不同程度上抑制脑损伤标志物的升高,但不能使其回落至基础值,分析原因一方面可能与剂量有关;另一方面可能是除炎性反应外,还有其他机制参与肝移植术诱发脑损伤。结合以上结论,静脉输注乌司他丁10000U/kg可减轻亲体肝移植术患儿。
[Abstract]:Objective: To observe the effect and mechanism of ulinastatin on brain injury in children with parent liver transplantation. Methods: 60 children with congenital biliary atresia, aged 6~10 months, weight 6.5~9.5kg, ASA grade II or III, B~C grade of liver function Child-Pugh classification, and the average age of donor 33 years (22-50 years old). All children were treated with combined general anesthesia. All the patients were treated with piggyback liver transplantation and left external leaves used for liver transplantation. According to the random digital table method, two groups (n=30) were randomly divided into the control group (group C) and ulinastatin group (group U). After anesthesia induction to the operation, ulinastatin was injected into Ulinastatin 100. 00U/kg, 0.9% Sodium Chloride Injection in the control group. After anesthesia induction (T1), 30 minutes (T2), 3 hours (T3) in the new liver period and 24 hours in the new liver period (T4), the concentration of S-100 beta protein and neuron specific enolase (NSE) in the serum of the children was detected by ELISA method, and the children were measured by radioimmunoassay. The concentration of interleukin -6 (IL-6), interleukin -10 (IL-10) and interleukin -18 (IL-18) in serum, heart rate, mean arterial pressure, central venous pressure and BIS value at all time points, and the awakening stage of children's delirium scale (Pediatric Anesthesia Emergence Delirium, PAED) and Bailey infant development scale, were used by trained physicians in hand. 1 days before the operation and second weeks after the operation, the children were graded on the nervous system, and the recovery of the children after operation and the intelligence and movement development of the children were evaluated. The results were as follows: the age of the 2 groups, the weight of the body, the duration of the operation, the duration of anesthesia, the anhepatic period, the amount of infusion and the amount of urine, the difference was not statistically significant (P0.05) there was no significant difference in S-100 beta concentration and NSE concentration in group.2 (P0.05). Compared with T1, the concentration of S-100 beta and NSE concentration increased (P0.05) at the 2 groups of T2,3 (P0.05), and there was no significant difference between the concentration of the beta and the concentration in T4. There was no statistically significant difference in serum IL-6, IL-10 and IL-18 concentration in.2 group T1 (P0.05). Compared with the control group, serum IL-6, IL-18 concentration decreased, serum IL-10 concentration increased (P0.05), and the difference was statistically significant when compared with the control group. The difference was statistically significant. The two groups of children were compared with the preoperative 1D, and the two groups of children had 2 weeks of intelligence and motor hair after operation. Compared with the C group, the motor development index (Psychomotor Development Index, PDI) had no statistical significance (P0.05), and the intellectual development index (Mental Development Index, MDI) decreased less (P0.05), PAED score decreased, and the waking period delirium score decreased, with statistical significance. The brain injury was the most serious in the new liver stage, and the level of serum S-100 beta and NSE was positively correlated with brain injury. The results showed that the levels of serum S-100 beta protein and NSE in the 2 groups were increased at T2 and T3, suggesting the parent body. The results of this study showed that serum S-100 beta protein and NSE levels, IL-6 and IL-18 concentrations decreased, serum IL-10 concentration increased, and ulinastatin could be used in different courses after T2,3. The degree of inhibition of the elevation of brain damage markers, but can not make it fall to the basic value, the analysis may be related to the dose related; on the other hand, other mechanisms may be involved in liver transplantation to induce brain damage. Combined with the above conclusion, intravenous infusion of ulinastatin 10000U/kg can reduce the number of children with liver transplantation.
【学位授予单位】:天津医科大学
【学位级别】:硕士
【学位授予年份】:2017
【分类号】:R726.1

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