手术伤害性刺激模型的18F-FDG PET脑功能成像研究

发布时间：2018-06-27 06:17

本文选题：跖肌手术 + 18F-FDG小动物PET　；参考：《北京协和医学院》2016年博士论文

【摘要】：前言：手术相关的疼痛是临床上最常见的疼痛类型之一,大约80%的手术患者经历了术后急性疼痛。伤害性刺激上传可能引起疼痛矩阵和学习记忆相关脑区的神经元兴奋性变化；或者同时诱发这些脑区神经源性炎症,参与术后认知功能障碍。正电子发射型计算机断层显像通过测量带放射性核素标记的物质如葡萄糖的代谢,可以反映大脑区域兴奋性的情况。本研究的目的是观察手术伤害性刺激对大脑功能代谢的影响,尤其是疼痛矩阵和学习记忆相关脑区的代谢变化。方法：本研究采用跖肌切口模型。在疼痛行为学测试部分,通过测量机械缩足阈值和热缩足潜伏期,对术后的疼痛行为进行评估。在PET影像学部分,分为手术伤害性刺激传入对大脑葡萄糖代谢的影响和跖肌手术术后大脑葡萄糖代谢的变化,观察术后不同时间葡萄糖代谢。18F-FDG PET图像使用统计参数图软件(Statistical Parametric Mapping, SPM)进行预处理和统计分析。结果：跖肌切口手术后,机械缩足阈值在术后1、4、12小时和术后第1、2天下降(p值均＜0.01)。热缩足潜伏期在术后1、4、12小时和术后第1、2、3天下降(术后1小时至1天,p＜0.01；术后第2、3天,p＜0.05)。在术后4小时,坐骨神经阻滞下跖肌手术大鼠的机械缩足阈值高于单纯跖肌手术组(p＜0.05)。在跖肌手术后1小时左右,下丘、小脑、延髓部分区域葡萄糖代谢增加。与单纯跖肌手术比较,罗哌卡因坐骨神经阻滞可以减弱小脑、中脑、延髓部分区域的葡萄糖代谢。术后第1天,双侧岛叶区域,对侧尾状壳核,同侧海马CA3和延髓部分区域葡萄糖代谢增加。术后第3天,对侧岛叶、对侧上丘、同侧下托部分区域葡萄糖代谢增加。术后第6天,双侧上丘,同侧第一躯体感觉皮层、丘脑和后压部皮层部分区域葡萄糖代谢增加。术后第9天,双侧丘脑、上丘、同侧外侧苍白球和内侧膝状体核以及小脑、延髓部分区域代谢增加。术后第15天,对侧纹状体、屏状核、上丘和下丘部分区域代谢增加。术后第21天,双侧听觉皮层,同侧丘脑、下丘,以及小脑、中脑、延髓部分区域代谢增加。扣带回葡萄糖代谢在术后第1天和第9天降低。前额叶和海马CA1区葡萄糖代谢在术后21天降低。罗哌卡因坐骨神经阻滞下减弱术后岛叶、尾状壳核、海马CA3区域、第一躯体感觉皮层、和丘脑等脑区葡萄糖代谢。结论：手术伤害性刺激上传至大脑,引起疼痛矩阵和学习记忆相关脑区葡萄糖代谢发生改变,其中岛叶、尾状壳核、海马CA3等脑区的激活。坐骨神经阻滞可以有效地减轻术后早期疼痛,并减弱手术伤害刺激对岛叶、尾状壳核、海马等脑区的激活。前言：围术期药物过敏反应发生率可以高达1：385,一旦发生,病情变化迅速,可严重威胁患者生命安全。有研究报道表明,手术麻醉过程中药物过敏导致3%至9.2%患者死亡。过敏反应发生时,及时正确的处理和其后续的过敏原检测十分重要。快速反应及时治疗有助于挽救患者生命。明确过敏药物,可以帮助患者在之后的手术麻醉中避免使用该药物,减少过敏反应发生的风险。尤其是在当今社会,老龄化趋势逐渐加重,人们接受手术治疗的可能性也大大增加。在我们的研究中,既往发生围术期局部麻醉或者全身麻醉下疑似药物过敏反应,或者既往多种食物药物严重过敏,需要在局部麻醉或者全身麻醉下检查或手术治疗而有发生围术期过敏反应风险的患者入组,进行皮内试验和/或嗜碱性粒细胞活化实验,结合患者病史,对疑似发生过敏反应者进行鉴别诊断,一方面获得国人围术期药物过敏反应的流行病学情况,另一方面通过检测过敏原,找到替代药物,减少患者再次发生过敏反应的风险,帮助患者顺利完成手术。方法：2009年9月至2016年1月,96名在既往局部麻醉或者全身麻醉过程中出现疑似药物过敏反应症状或者由于自身过敏体质的患者进入试验,进行皮内测试和(或)嗜碱性粒细胞活化实验,寻找可能的过敏原。测试药物的选择依据麻醉单记录中用到的麻醉药物,同时选择记录单以外的同类药物作为可能的替代药物进行检测。患者发生反应时的症状、发生反应时间和使用药物结合皮内试验和嗜碱性粒细胞活化实验的结果用来判定围术期药物过敏反应的存在及判定药物过敏原。皮内试验使用0.9%生理盐水作为阴性对照；使用10mg/ml组胺溶液作为阳性对照；待检测药物稀释至1：1000(注：肌松药及吗啡为1：10000稀释液)。在患者前臂、上臂或者后背注射0.02-0.03ml药液,产生直径约为3mm注射皮丘,15分钟后记录皮丘及红晕的最大直径和垂直直径。阳性结果判断标准：注射部位周围出现红斑丘疹且伴有红晕,风团直径大于等于8mm,或者至少为注射直径2倍。活化的嗜碱性粒细胞比例≥5%且刺激指数SI(SI=药物活化的嗜碱性粒细胞比例/阴性质控活化的嗜碱性粒细胞比例)≥2,作为药物检测的阳性标准。结果：在进入研究的96名患者中,39名患者由于既往在全身麻醉下或者静脉麻醉下围术期发生疑似过敏反应而就诊；42名患者由于既往局部麻醉下围术期发生疑似过敏反应而就诊；15名患者既往未发生局部麻醉或全身麻醉不良反应,但是由于多种药物食物严重过敏且有手术麻醉需求而要求进行麻醉过敏原检测。既往发生过疑似过敏反应的81名患者中,一共有36名患者确诊发生了药物过敏反应,其中女性23名,男性13名,女性是男性的1.8倍。36名患者患者中,31名患者在全身麻醉或者静脉麻醉过程中发生过敏反应,5名患者在局部麻醉下发生过敏反应,全身麻醉下发生的过敏反应是局部麻醉下过敏反应的6.2倍。全身麻醉下发生过敏反应的31名患者,有2名患者分别发生2次过敏反应,因此共发生了33次围术期过敏反应。在全身麻醉下围术期过敏反应中,抗生素过敏者8例,肌松药过敏者7例,咪达唑仑过敏者5例,异丙酚过敏者3例,依托咪酯过敏者1例,舒芬太尼过敏者3例,安定过敏者1例。利多卡因过敏者1例。琥珀酰明胶过敏者3例。局部麻醉药物过敏的5人中,利多卡因过敏者3例,其中1例同时对阿替卡因过敏,罗哌卡因过敏者2例。共38名患者顺利手术,其中由于既往在全身麻醉下或者静脉麻醉下围术期发生疑似过敏反应而就诊的患者中,20名患者顺利再次手术；由于既往局部麻醉下围术期发生疑似过敏反应而就诊的患者中,11名顺利再次手术；既往未发生局部麻醉或全身麻醉不良反应而进行麻醉药物过敏原检测的患者中,7名患者顺利手术。结论：在围术期过敏反应中,女性患者多于男性,女性是男性的女性是男性的1.8倍。在全麻麻醉诱导的过敏反应中,78.8%发生在诱导阶段；91%出现了心血管症状；抗生素和肌松药是最主要的过敏原。
[Abstract]:Preface: surgery related pain is one of the most common types of pain in the clinic. About 80% of the patients experienced acute postoperative pain. The uploading of nociceptive stimuli may cause excitatory changes in the pain matrix and learning memory related brain regions, or induce neurogenic inflammation in these brain regions and participate in post-operative cognitive work. Energy barriers. Positron emission computed tomography (positron emission computed tomography) can reflect brain regional excitability by measuring the metabolism of radioactive nuclide labeled substances such as glucose. The purpose of this study is to observe the effects of surgical nociceptive stimuli on brain function metabolism, especially the pain matrix and the metabolic changes in the learning and memory related brain regions. Methods: the metatarsal muscle incision model was used in this study. In the pain behavioral test part, the postoperative pain behavior was evaluated by measuring the threshold of mechanical contraction and the latent period of thermal contraction. In the PET imaging part, the effects of surgical nociceptive stimulus on brain glucose metabolism and brain glucose metabolism after the operation of metatarsal muscle were divided. The.18F-FDG PET image of glucose metabolism (Statistical Parametric Mapping, SPM) was pretreated and statistically analyzed at different time after the operation. Results: after the operation of the metatarsal muscle incision, the threshold of mechanical contraction was reduced at 1,4,12 hours after operation and the postoperative 1,2 under the operation (P < 0.01). The latent period of the heat contraction foot was performed. After 1,4,12 hours and 1,2,3 days after operation (1 hours to 1 days after operation, P < 0.01 and P < 0.05 after operation 2,3), the threshold of mechanical contraction of rats with metatarsal muscles under the sciatic nerve block was higher than that of the simple metatarsal muscle group (P 0.05) at 4 hours after the operation (P < 0.05). The dextrose of the inferior colliculus, cerebellum, and the medullary part of the medulla after the operation of the metatarsal muscle was Xie Zeng Plus. Compared with simple metatarsal muscle surgery, ropivacaine block can weaken glucose metabolism in the cerebellum, midbrain, and medulla. On the first day after operation, the glucose metabolism in the lateral caudal putamen, the ipsilateral hippocampal CA3 and the medulla is increased. On the third day after the operation, the lateral Island leaves, the lateral superior colliculus, and the ipsilateral underlay areas. Glucose metabolism increased. On the sixth day after operation, glucose metabolism increased in the bilateral superior colliculus, the same lateral first somatosensory cortex, the thalamus and the posterior pressure cortex. On the ninth day after the operation, the bilateral thalamus, upper colliculus, the lateral pallidus and medial geniculate nucleus, and the cerebellum, and the medullary part of the cerebellum were increased. Fifteenth days after operation, the contralateral striatum, the screen nucleus, Metabolism of the upper colliculus and inferior colliculus increased. On the twenty-first day after the operation, the bilateral auditory cortex, the ipsilateral thalamus, the hypothalamus, the cerebellum, the midbrain, and the medulla were increased. The glucose metabolism in the cingulate gyrus decreased at first days and ninth days after operation. The glucose metabolism in the prefrontal and hippocampal CA1 areas decreased at 21 days after operation. Glucose metabolism in the insula, caudate putamen, caudate putamen, CA3 region of the hippocampus, the first somatosensory cortex, and thalamus. Conclusion: surgical nociceptive stimulation is uploaded to the brain, causing changes in the glucose metabolism in the pain matrix and learning memory related brain regions, including the activation of the insula, caudate putamen, and the hippocampus CA3. Sciatic nerve block can be used. In order to effectively relieve early postoperative pain and reduce the activation of surgical injury stimulation to the insula, caudate putamen nucleus and hippocampus. Preface: the incidence of anaphylaxis in the perioperative period can be as high as 1:385. Once the disease occurs, the disease changes rapidly and can seriously threaten the patient's life safety. It is important to cause 3% to 9.2% deaths. Timely and correct treatment and subsequent allergen detection are important. Quick response and timely treatment help to save the patient's life. In today's society, the aging trend is increasing, and the possibility of undergoing surgical treatment has also increased greatly. In our study, we have had previous perioperative local or general anesthesia, suspected drug anaphylaxis, or a number of previous food drugs with severe allergies, which need to be examined under local or general anesthesia or treated by surgery. The patients who had the risk of allergic reaction during the perioperative period were treated with intradermal tests and / or basophil activation tests, combined with the patient's history, the differential diagnosis of suspected anaphylaxis, on the one hand, the epidemiological situation of the drug allergic reaction in the Chinese perioperative period was obtained, and on the other hand, an alternative was found by detecting allergens. Drugs, to reduce the risk of anaphylaxis in patients, help patients successfully complete the operation. Methods: from September 2009 to January 2016, 96 patients who had suspected drug allergy symptoms during previous local or general anesthesia, or patients with their own allergies, were tested for intradermal tests and (or) basophils. Cell activation experiments, search for possible allergens. Test the choice of drugs based on narcotic drugs used in the narcotic record, and select similar drugs other than the recording sheet as possible alternative drugs. The symptoms of the patients, the time of the reaction and the combination of the intradermal test and the basophil activity with the drug. The results were used to determine the presence of the drug allergy in the perioperative period and to determine the drug allergen. The intradermal test used 0.9% normal saline as a negative control; 10mg/ml histamine solution was used as a positive control; the drug was diluted to 1:1000 (muscle relaxant and morphine 1: 10000 dilution). In the forearm, upper arm or The 0.02-0.03ml liquid was injected into the back of the back and the diameter of the mound was injected about 3mm. The maximum diameter and the vertical diameter of the skin and red halo were recorded 15 minutes later. The positive results were as follows: the erythema papule around the injection site was accompanied by a red halo, the diameter of the wind mass was more than equal to that of 8mm, or the diameter of the injection was 2 times less. More than 5% and the stimulus index SI (SI= activated basophil ratio / negative quality basophil ratio) was more than 2, as a positive standard for drug detection. Results: among the 96 patients entering the study, 39 patients had suspected allergic reactions in the perioperative period under general anesthesia or intravenous anesthesia. 42 patients were diagnosed with suspected anaphylaxis due to previous local anesthesia; 15 patients had no previous local anaesthesia or general anaesthesia, but 81 were suspected of anaphylaxis due to severe food allergies and surgical anesthesia requirements. In a total of 36 patients, a total of 36 patients were diagnosed with anaphylaxis, of which 23 were female, 13 men were male, and women were 1.8 times of male.36 patients. 31 patients had anaphylaxis during general anesthesia or intravenous anesthesia, 5 patients had anaphylaxis under local anaesthesia, and allergic reactions under general anesthesia were caused by anaphylaxis. 6.2 times of anaphylaxis under local anaesthesia. In 31 patients with anaphylaxis under general anaesthesia, 2 patients had 2 anaphylaxis, thus a total of 33 perioperative anaphylaxis. In the perioperative anaphylaxis, 8 cases of antibiotic allergies, 7 cases of muscle relaxant allergies, 5 cases of midazolam allergy, and propofol over the perioperative anaphylaxis. In 3 sensitized patients, 1 were allergic to etomidate, 3 were hypersensitive to sufentanil, 1 were allergic to anaphylaxis, 1 cases of lidocaine allergy. 3 cases of succinyl gelatin allergy. 5 of local anesthetic allergies and 3 cases of lidocaine allergy, of which 1 cases were allergic to altecaine and 2 cases were allergic to ropivacaine. A total of 38 patients were operated successfully, among them, a total of 38 patients were operated successfully. Of the patients who had previously suspected allergic reactions under general anesthesia or intravenous anesthesia, 20 patients were reoperated again; 11 of the patients who had been diagnosed with suspected anaphylaxis during the perioperative period of local anesthesia were reoperated again; there were no previous local or general anesthesia adverse reactions. In patients with anaphylactic anaphylaxis, 7 patients were successfully operated. Conclusion: during the perioperative anaphylaxis, women were more than men, women were 1.8 times as long as men and 78.8% were induced in the anaphylaxis induced anaphylaxis; 91% had cardiovascular symptoms, antibiotics and muscle relaxants. It's the most important allergens.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R614

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