本文選題：右美托咪定 + 胰島素��； 參考：《鄭州大學》2014年碩士論文

【摘要】：背景與目的 右美托咪定（Dexmedetomidine，Dex）屬于咪唑類的衍生物，是美托咪定的右旋異構(gòu)體，一種新型高選擇性的α2腎上腺素能受體激動劑，具有鎮(zhèn)痛、鎮(zhèn)靜、抗焦慮、催眠、遺忘和交感神經(jīng)抑制等作用；最新的研究表明，右美托咪定還有一定的抗炎、抗應(yīng)激等作用。右美托咪定能夠維持血流動力學穩(wěn)定，對呼吸無抑制作用，對心、腦、腎等器官功能能產(chǎn)生一定的保護作用[1、2]。自1999年被美國食品藥品管理局(Food and Drug Administration， FDA)批準用于成人重癥監(jiān)護病房(ICU)機械通氣患者短期鎮(zhèn)靜以來，右美托咪定因其獨特的藥理學特性，在國內(nèi)、外已被廣泛應(yīng)用。 目前，國內(nèi)、外多項研究[3、4、5、6、7]表明，右美托咪定具有抑制應(yīng)激反應(yīng)、維持血流動力學穩(wěn)定、抑制拔管刺激、減少術(shù)后躁動等作用；且右美托咪定有保持顱內(nèi)穩(wěn)態(tài)平衡、易喚醒、甚至能在手術(shù)室允許神經(jīng)功能評定、減少顱內(nèi)血流(維持氧供需平衡)和腦保護功能；這對神經(jīng)外科患者來說是非常有利的，因此其在神經(jīng)外科手術(shù)患者中已被廣泛應(yīng)用。 近期，有研究表明：對試驗用犬予以右美托咪定鎮(zhèn)靜，右美托咪定能顯著升高血糖，抑制胰島素的釋放，增加血漿乳酸濃度，降低血漿皮質(zhì)醇濃度[8、9、10]。右美托咪定的這些作用對神經(jīng)外科手術(shù)患者來說是不利的：高血糖會導致血漿滲透壓改變，從而影響組織細胞的形態(tài)和功能，并且通過抑制免疫、上調(diào)促炎因子、損害線粒體功能和增加氧自由基的生成而損害機體組織器官。圍術(shù)期高血糖可引起大多數(shù)類型的腦缺血程度惡化，并且已經(jīng)證實右美托咪定對心血管內(nèi)皮細胞有一定的損傷作用。乳酸是糖酵解的代謝產(chǎn)物之一，一直被認為是中樞神經(jīng)系統(tǒng)缺血、缺氧或損傷的標志物，臨床上乳酸檢測的主要功能是判斷缺血細胞的死亡程度。皮質(zhì)醇是一種類固醇激素，是應(yīng)激反應(yīng)的標志性產(chǎn)物之一，具有調(diào)節(jié)機體內(nèi)環(huán)境的重要作用[11]。 神經(jīng)外科手術(shù)患者，由于其操作的精細度要求，常需要較深的麻醉深度。麻醉過深或麻醉過淺對患者來說都是不利的。隨著臨床上新的肌松藥和新的鎮(zhèn)靜、鎮(zhèn)痛藥的聯(lián)合應(yīng)用，全身麻醉的麻醉深度、意識狀態(tài)常常會被掩蓋或難以識別，因此，控制并判斷相對合適的麻醉深度已成為亟待解決的臨床問題。NT指數(shù)（Narcotrend Index）是一種新的潛力巨大的麻醉深度監(jiān)測方法。由于其電極安放位置沒有特殊要求，且能夠?qū)崟r監(jiān)測，決定了其能在神經(jīng)外科患者中使用。 目前，有關(guān)右美托咪定對血糖、胰島素、皮質(zhì)醇、乳酸影響的研究為數(shù)不多，且國內(nèi)外的研究結(jié)果不盡相同。本研究就兩種劑量右美托咪定對神經(jīng)外科患者術(shù)中血糖、胰島素、皮質(zhì)醇、乳酸的影響進行探討，，來為臨床上合理用藥提供依據(jù)。 材料與方法 納入擇期全麻下行聽神經(jīng)瘤切除的患者60例，年齡20～60歲， ASA分級Ⅰ～Ⅱ級，體重50～80kg，采用隨機數(shù)字表法，將其隨機分為3組： C組（對照組）、D1組（Dex0.3μg/kg/h組）、D2組（Dex0.5μg/kg/h組），每組20例。 麻醉誘導：D1組麻醉誘導前10分鐘用微量泵持續(xù)靜脈泵入鹽酸右美托咪定0.3μg/kg，之后以0.3μg/kg/h的速度泵注；D2組麻醉誘導前10分鐘微量泵持續(xù)靜脈泵入鹽酸右美托咪定0.5μg/kg，之后以0.5μg/kg/h的速度泵注； N組則泵入等量生理鹽水。泵注完畢后開啟丙泊酚TCI輸注泵，按照序貫法進行血漿靶控輸注。三組患者NT指數(shù)降至35%左右后，靜脈注射芬太尼4μg/kg、順式阿曲庫銨0.2mg/kg，手動通氣至當肌肉完全松弛，用普通直接喉鏡行氣管插管。麻醉維持：丙泊酚TCI+瑞芬太尼0.2μg/(kg·min)，監(jiān)測并維持NT指數(shù)在30-40%，術(shù)中間斷靜脈注射順式阿曲庫銨0.07mg/kg，所有患者均術(shù)后常規(guī)鎮(zhèn)痛。 觀察并記錄患者入室時（T0）、氣管插管前（T1）、氣管插管后即刻（T2）、氣管插管后3分鐘（T3）、手術(shù)開始1小時（T4）、手術(shù)開始2小時時（T5）、術(shù)畢（T6）等7個時間點的收縮壓（SBP）、舒張壓（DBP）、平均動脈壓（MAP）、心率（HR）、脈搏氧飽和度（SPO2）、Narcotrend Index(NT指數(shù))、及呼氣末二氧化碳濃度(PETCO2)；并記錄患者意識消失時的丙泊酚靶濃度。各組患者于上述7個時間點測定動脈血氣，檢測乳酸、血糖含量，并于上述7個時間點分別抽取中心靜脈血3ml，注入抗凝管中，在4℃、3000r/min條件下離心15分鐘，留取上清液于EP管，并于—80℃超低溫冰箱中保存待用。采用酶聯(lián)免疫吸附法（ELISA）測定血漿胰島素（Ins）、皮質(zhì)醇（Cor）的濃度。 運用SPSS17.0軟件進行統(tǒng)計學分析，所有定量資料均以均數(shù)±標準差（x±s）表示，定量資料的分析采用t檢驗或校正的t檢驗、卡方檢驗，多組定量資料的比較采用單因素方差分析、重復測量。檢驗水準：α=0.05。 結(jié)果 1．三組患者一般情況比較。 三組患者年齡、體重、性別構(gòu)成比及手術(shù)時間的組間比較，差異無統(tǒng)計學意義（p＞0.05）。 2．三組各個時間點NT指數(shù)的比較。 與C組相比，D1、D2組在T2時間點（插管后即刻）均明顯較低，且差異有統(tǒng)計學意義（p＜0.05）。 3．三組患者丙泊酚靶濃度的比較。 與C組相比，D1組和D2組患者NT指數(shù)降至35%左右時丙泊酚的血漿靶濃度均較低，且差異有統(tǒng)計學意義（p＜0.05）；D2組患者低于D1組患者（p＜0.05）。 4．三組患者術(shù)中生命體征的比較。 組內(nèi)比較：與T0時間相比，C組和D1組T1、T4、T5時間MAP、SBP、DBP、HR均降低,且差異有統(tǒng)計學意義(p＜0.05)，D2組在T1、T3、T4、T5時間MAP、SBP、DBP、HR均降低，且差異有統(tǒng)計學意義(p＜0.05)，C組T2時間SBP升高，且差異有統(tǒng)計學意義（p＜0.05）；三組各時間點時間SpO2則差異無統(tǒng)計學意義（p＞0.05）。組間比較：三組之間基礎(chǔ)MAP、SBP、DBP、HR、SpO2的差異無統(tǒng)計學意義（p＞0.05）；D1、D2組在T2、T3時間MAP、SBP、DBP、HR較C組低，且差異有統(tǒng)計學意義(p＜0.05)。 5．三組患者血糖、胰島素、皮質(zhì)醇、乳酸的比較。 C組、D1、D2組血糖、胰島素、皮質(zhì)醇、乳酸在各時間點組間、組內(nèi)比較差異均無統(tǒng)計學意義（p＞0.05）。 結(jié)論 1．右美托咪定能夠減少誘導時丙泊酚的血漿靶濃度，與右美托咪定劑量有相關(guān)性。 2．右美托咪定能一定程度的抑制應(yīng)激反應(yīng)，能維持患者術(shù)中NT指數(shù)和血流動力學的穩(wěn)定。 3．右美托咪定不減少胰島素釋放量，不增加術(shù)中血糖濃度，對皮質(zhì)醇、乳酸無明顯影響。
[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.
【學位授予單位】：鄭州大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R614

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