右美托咪定对听神经瘤切除术患者术中胰岛素、血糖、皮质醇水平的影响

发布时间：2018-06-23 01:01

本文选题：右美托咪定 + 胰岛素　；参考：《郑州大学》2014年硕士论文

【摘要】：背景与目的右美托咪定（Dexmedetomidine，Dex）属于咪唑类的衍生物，是美托咪定的右旋异构体，一种新型高选择性的α2肾上腺素能受体激动剂，具有镇痛、镇静、抗焦虑、催眠、遗忘和交感神经抑制等作用；最新的研究表明，右美托咪定还有一定的抗炎、抗应激等作用。右美托咪定能够维持血流动力学稳定，对呼吸无抑制作用，对心、脑、肾等器官功能能产生一定的保护作用[1、2]。自1999年被美国食品药品管理局(Food and Drug Administration， FDA)批准用于成人重症监护病房(ICU)机械通气患者短期镇静以来，右美托咪定因其独特的药理学特性，在国内、外已被广泛应用。目前，国内、外多项研究[3、4、5、6、7]表明，右美托咪定具有抑制应激反应、维持血流动力学稳定、抑制拔管刺激、减少术后躁动等作用；且右美托咪定有保持颅内稳态平衡、易唤醒、甚至能在手术室允许神经功能评定、减少颅内血流(维持氧供需平衡)和脑保护功能；这对神经外科患者来说是非常有利的，因此其在神经外科手术患者中已被广泛应用。近期，有研究表明：对试验用犬予以右美托咪定镇静，右美托咪定能显著升高血糖，抑制胰岛素的释放，增加血浆乳酸浓度，降低血浆皮质醇浓度[8、9、10]。右美托咪定的这些作用对神经外科手术患者来说是不利的：高血糖会导致血浆渗透压改变，从而影响组织细胞的形态和功能，并且通过抑制免疫、上调促炎因子、损害线粒体功能和增加氧自由基的生成而损害机体组织器官。围术期高血糖可引起大多数类型的脑缺血程度恶化，并且已经证实右美托咪定对心血管内皮细胞有一定的损伤作用。乳酸是糖酵解的代谢产物之一，一直被认为是中枢神经系统缺血、缺氧或损伤的标志物，临床上乳酸检测的主要功能是判断缺血细胞的死亡程度。皮质醇是一种类固醇激素，是应激反应的标志性产物之一，具有调节机体内环境的重要作用[11]。神经外科手术患者，由于其操作的精细度要求，常需要较深的麻醉深度。麻醉过深或麻醉过浅对患者来说都是不利的。随着临床上新的肌松药和新的镇静、镇痛药的联合应用，全身麻醉的麻醉深度、意识状态常常会被掩盖或难以识别，因此，控制并判断相对合适的麻醉深度已成为亟待解决的临床问题。NT指数（Narcotrend Index）是一种新的潜力巨大的麻醉深度监测方法。由于其电极安放位置没有特殊要求，且能够实时监测，决定了其能在神经外科患者中使用。目前，有关右美托咪定对血糖、胰岛素、皮质醇、乳酸影响的研究为数不多，且国内外的研究结果不尽相同。本研究就两种剂量右美托咪定对神经外科患者术中血糖、胰岛素、皮质醇、乳酸的影响进行探讨，，来为临床上合理用药提供依据。材料与方法纳入择期全麻下行听神经瘤切除的患者60例，年龄20～60岁， ASA分级Ⅰ～Ⅱ级，体重50～80kg，采用随机数字表法，将其随机分为3组： C组（对照组）、D1组（Dex0.3μg/kg/h组）、D2组（Dex0.5μg/kg/h组），每组20例。麻醉诱导：D1组麻醉诱导前10分钟用微量泵持续静脉泵入盐酸右美托咪定0.3μg/kg，之后以0.3μg/kg/h的速度泵注；D2组麻醉诱导前10分钟微量泵持续静脉泵入盐酸右美托咪定0.5μg/kg，之后以0.5μg/kg/h的速度泵注； N组则泵入等量生理盐水。泵注完毕后开启丙泊酚TCI输注泵，按照序贯法进行血浆靶控输注。三组患者NT指数降至35%左右后，静脉注射芬太尼4μg/kg、顺式阿曲库铵0.2mg/kg，手动通气至当肌肉完全松弛，用普通直接喉镜行气管插管。麻醉维持：丙泊酚TCI+瑞芬太尼0.2μg/(kg·min)，监测并维持NT指数在30-40%，术中间断静脉注射顺式阿曲库铵0.07mg/kg，所有患者均术后常规镇痛。观察并记录患者入室时（T0）、气管插管前（T1）、气管插管后即刻（T2）、气管插管后3分钟（T3）、手术开始1小时（T4）、手术开始2小时时（T5）、术毕（T6）等7个时间点的收缩压（SBP）、舒张压（DBP）、平均动脉压（MAP）、心率（HR）、脉搏氧饱和度（SPO2）、Narcotrend Index(NT指数)、及呼气末二氧化碳浓度(PETCO2)；并记录患者意识消失时的丙泊酚靶浓度。各组患者于上述7个时间点测定动脉血气，检测乳酸、血糖含量，并于上述7个时间点分别抽取中心静脉血3ml，注入抗凝管中，在4℃、3000r/min条件下离心15分钟，留取上清液于EP管，并于—80℃超低温冰箱中保存待用。采用酶联免疫吸附法（ELISA）测定血浆胰岛素（Ins）、皮质醇（Cor）的浓度。运用SPSS17.0软件进行统计学分析，所有定量资料均以均数±标准差（x±s）表示，定量资料的分析采用t检验或校正的t检验、卡方检验，多组定量资料的比较采用单因素方差分析、重复测量。检验水准：α=0.05。结果 1．三组患者一般情况比较。三组患者年龄、体重、性别构成比及手术时间的组间比较，差异无统计学意义（p＞0.05）。 2．三组各个时间点NT指数的比较。与C组相比，D1、D2组在T2时间点（插管后即刻）均明显较低，且差异有统计学意义（p＜0.05）。 3．三组患者丙泊酚靶浓度的比较。与C组相比，D1组和D2组患者NT指数降至35%左右时丙泊酚的血浆靶浓度均较低，且差异有统计学意义（p＜0.05）；D2组患者低于D1组患者（p＜0.05）。 4．三组患者术中生命体征的比较。组内比较：与T0时间相比，C组和D1组T1、T4、T5时间MAP、SBP、DBP、HR均降低,且差异有统计学意义(p＜0.05)，D2组在T1、T3、T4、T5时间MAP、SBP、DBP、HR均降低，且差异有统计学意义(p＜0.05)，C组T2时间SBP升高，且差异有统计学意义（p＜0.05）；三组各时间点时间SpO2则差异无统计学意义（p＞0.05）。组间比较：三组之间基础MAP、SBP、DBP、HR、SpO2的差异无统计学意义（p＞0.05）；D1、D2组在T2、T3时间MAP、SBP、DBP、HR较C组低，且差异有统计学意义(p＜0.05)。 5．三组患者血糖、胰岛素、皮质醇、乳酸的比较。 C组、D1、D2组血糖、胰岛素、皮质醇、乳酸在各时间点组间、组内比较差异均无统计学意义（p＞0.05）。结论 1．右美托咪定能够减少诱导时丙泊酚的血浆靶浓度，与右美托咪定剂量有相关性。 2．右美托咪定能一定程度的抑制应激反应，能维持患者术中NT指数和血流动力学的稳定。 3．右美托咪定不减少胰岛素释放量，不增加术中血糖浓度，对皮质醇、乳酸无明显影响。
[Abstract]:Background and purpose
Dexmedetomidine (Dex), a derivative of imidazole, is a dexameptic dextral isomer, a novel highly selective alpha 2 adrenergic receptor agonist, with analgesic, sedative, antianxiety, hypnotic, amnesia, and sympathetic inhibitory effects. The latest study shows that right metomomidin has some anti-inflammatory and anti inflammatory effects. Dexmedetomidin can maintain hemodynamic stability, have no inhibitory effect on respiration, and have certain protective effects on heart, brain, kidney and other organs function [1,2]. was approved by the Food and Drug Administration (FDA) in 1999 for the short-term town of mechanical ventilation patients in the adult intensive care unit (ICU). Since its establishment, dexmedetomidine has been widely used in China and abroad due to its unique pharmacological characteristics.
At present, a number of studies at home and abroad have shown that dexmedetomidin has the effect of inhibiting stress response, maintaining hemodynamic stability, inhibiting extubation stimulation and reducing postoperative restlessness, and right metomomidin has a stable homeostasis of intracranial homeostasis, easy to wake up, and even allow neurological assessment in the operation room to reduce intracranial blood flow (maintenance of oxygen supply). Need balance) and brain protection function, which is very beneficial to patients in Department of Neurosurgery, so it has been widely used in patients undergoing Department of Neurosurgery surgery.
Recent studies have shown that right metomomidine was used in trial dogs. Dexmedetomidine could significantly increase blood sugar, inhibit insulin release, increase plasma lactic acid concentration, and reduce the plasma cortisol concentration [8,9,10]. dexmedetomidin's effects on patients in Department of neurosurgery: hyperglycemia may lead to plasma osmosis Pressure changes, which affect the morphology and function of tissue cells, and damage the tissues and organs by inhibiting immunity, increasing proinflammatory factors, damaging mitochondrial function and increasing the formation of oxygen free radicals. Perioperative hyperglycemia may cause most types of cerebral ischemia to deteriorate, and right metoimidine has been proved to be fine to cardiovascular endothelium. Lactic acid is one of the metabolites of glycolysis, which has been considered as a marker of ischemia, hypoxia or injury in the central nervous system. The main function of the clinical lactic acid detection is to judge the degree of death of the ischemic cells. Cortisol is a steroid hormone, one of the marker products of stress response, and is regulated. The important role of the body environment in the body [11].
The patients in the Department of Neurosurgery often need a deeper depth of anesthesia because of the precision of their operation. Too deep or too shallow is adverse to the patients. With the new clinical muscle relaxants and new sedative, combined use of analgesics, the depth of general anesthesia, the state of consciousness is often obscured or difficult to identify. The.NT index (Narcotrend Index), which is an urgent clinical problem, is a new and potential method for monitoring the depth of anesthesia. It is a new method for monitoring the depth of anaesthesia. It can be used in Department of neurosurgery patients because the location of the electrode is not special and can be monitored in real time.
At present, there are few studies on the effects of dexmedetomidine on blood glucose, insulin, cortisol and lactic acid, and the results are not the same at home and abroad. Two doses of dexmedetomidine are used to investigate the effects of blood glucose, insulin, cortisol and lactic acid in the patients in Department of neurosurgery to provide the basis for clinical rational use.
Materials and methods
60 patients, aged 20~60 years old, ASA grade I to grade II, weight 50 ~ 80kg, were randomly divided into 3 groups: group C (control group), group D1 (Dex0.3 mug g/kg/h group), group D2 (Dex0.5 u g/kg/h group), 20 cases in each group.
Anesthesia induction: 10 minutes before induction of anesthesia induction in group D1, a micropump was pumped into right metomomimidin 0.3 u g/kg, and then pumped at 0.3 u g/kg/h; 10 minutes before induction of anesthesia in group D2, the micropump was pumped into right metomomidine hydrochloride 0.5 um g/kg and then pumped at 0.5 mu g/kg/h; the N group was pumped into the same amount of physiological saline. After the pump was completed, the propofol TCI infusion pump was opened and the plasma target controlled infusion was carried out according to the sequential method. After the NT index of the three groups was reduced to about 35%, the intravenous fentanyl 4 mu g/kg, CIS atracurium 0.2mg/kg, the manual ventilation was completely relaxed and the tracheal intubation was performed by ordinary direct laryngoscope. Anesthesia maintenance: Propofol TCI+ remifentanil 0.2 uits (kg. Min), the NT index was monitored and maintained at 30-40%, and CIS atracurium 0.07mg/kg was injected into the middle of the operation. All patients received routine analgesia after operation.
At the time of admission (T0), before endotracheal intubation (T1), immediately after tracheal intubation (T2), 3 minutes after endotracheal intubation (T3), 1 hours after the operation (T4), 2 hours of operation (T5), SBP, diastolic pressure (DBP), mean arterial pressure (MAP), heart rate (HR), pulse oxygen saturation (SPO2) The concentration of propofol at the end of expiratory carbon dioxide (PETCO2), and the concentration of propofol target when the patient's consciousness disappeared. The arterial blood gas was measured at the 7 time points above, and the contents of lactic acid and blood sugar were measured, and the central venous blood 3ml was extracted at the 7 time points above, and the blood was injected into the anticoagulant tube and kept at 4 and 3000r/min for 15 minutes. The supernatant was stored in the EP tube and stored in an ultra low temperature refrigerator at 80 degree. The plasma insulin (Ins) and cortisol (Cor) concentration were measured by enzyme linked immunosorbent assay (ELISA).
Statistical analysis was carried out with SPSS17.0 software. All quantitative data were expressed with mean mean + standard deviation (x + s). Quantitative data were analyzed by t test or corrected t test, chi square test, and multiple quantitative data were compared by single factor analysis of variance and repeated measurement. Test water accuracy: alpha =0.05.
Result
1. the general situation of the three groups was compared.
There was no significant difference in age, weight, sex ratio and operative time between the three groups (P > 0.05).
2. comparison of the NT index at each time point in the three groups.
Compared with group C, D1 and D2 groups were significantly lower at T2 time points (immediately after intubation), and the difference was statistically significant (P < 0.05).
3. comparison of target concentration of propofol in three groups of patients.
Compared with the C group, the plasma target concentration of propofol was lower when the NT index decreased to about 35% in the D1 group and the D2 group, and the difference was statistically significant (P < 0.05), and the patients in the group D2 were lower than those in the D1 group (P < 0.05).
4. the comparison of the vital signs during the operation of the three groups.
Compared with T0 time, T1, T4, T5 time, MAP, SBP, DBP, HR in group C and D1 were reduced, and the difference was statistically significant (P < 0.05). The difference was not statistically significant (P > 0.05). There was no statistical difference between the three groups (P > 0.05) between the three groups (P > 0.05); D1, D2 group was in T2, T3 time MAP, DBP, and the difference was statistically significant (0.05).
5. comparison of blood glucose, insulin, cortisol and lactic acid between the three groups.
Blood glucose, insulin, cortisol and lactic acid in group C, group D1 and group D2 had no significant difference at each time point (P > 0.05).
conclusion
1. dexmedetomidine can reduce the plasma target concentration of propofol during induction, which is related to the dose of dexmedetomidine.
2. dexmedetomidine can inhibit the stress response to a certain extent, and maintain the NT index and hemodynamic stability during operation.
3. dexmedetomidine did not reduce insulin release and did not increase intraoperative blood glucose concentration, but had no significant effect on cortisol and lactic acid.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R614

【参考文献】