手術(shù)傷害性刺激模型的18F-FDG PET腦功能成像研究
本文選題:跖肌手術(shù) + 18F-FDG小動物PET ; 參考:《北京協(xié)和醫(yī)學(xué)院》2016年博士論文
【摘要】:前言:手術(shù)相關(guān)的疼痛是臨床上最常見的疼痛類型之一,大約80%的手術(shù)患者經(jīng)歷了術(shù)后急性疼痛。傷害性刺激上傳可能引起疼痛矩陣和學(xué)習(xí)記憶相關(guān)腦區(qū)的神經(jīng)元興奮性變化;或者同時誘發(fā)這些腦區(qū)神經(jīng)源性炎癥,參與術(shù)后認(rèn)知功能障礙。正電子發(fā)射型計算機(jī)斷層顯像通過測量帶放射性核素標(biāo)記的物質(zhì)如葡萄糖的代謝,可以反映大腦區(qū)域興奮性的情況。本研究的目的是觀察手術(shù)傷害性刺激對大腦功能代謝的影響,尤其是疼痛矩陣和學(xué)習(xí)記憶相關(guān)腦區(qū)的代謝變化。方法:本研究采用跖肌切口模型。在疼痛行為學(xué)測試部分,通過測量機(jī)械縮足閾值和熱縮足潛伏期,對術(shù)后的疼痛行為進(jìn)行評估。在PET影像學(xué)部分,分為手術(shù)傷害性刺激傳入對大腦葡萄糖代謝的影響和跖肌手術(shù)術(shù)后大腦葡萄糖代謝的變化,觀察術(shù)后不同時間葡萄糖代謝。18F-FDG PET圖像使用統(tǒng)計參數(shù)圖軟件(Statistical Parametric Mapping, SPM)進(jìn)行預(yù)處理和統(tǒng)計分析。結(jié)果:跖肌切口手術(shù)后,機(jī)械縮足閾值在術(shù)后1、4、12小時和術(shù)后第1、2天下降(p值均<0.01)。熱縮足潛伏期在術(shù)后1、4、12小時和術(shù)后第1、2、3天下降(術(shù)后1小時至1天,p<0.01;術(shù)后第2、3天,p<0.05)。在術(shù)后4小時,坐骨神經(jīng)阻滯下跖肌手術(shù)大鼠的機(jī)械縮足閾值高于單純跖肌手術(shù)組(p<0.05)。在跖肌手術(shù)后1小時左右,下丘、小腦、延髓部分區(qū)域葡萄糖代謝增加。與單純跖肌手術(shù)比較,羅哌卡因坐骨神經(jīng)阻滯可以減弱小腦、中腦、延髓部分區(qū)域的葡萄糖代謝。術(shù)后第1天,雙側(cè)島葉區(qū)域,對側(cè)尾狀殼核,同側(cè)海馬CA3和延髓部分區(qū)域葡萄糖代謝增加。術(shù)后第3天,對側(cè)島葉、對側(cè)上丘、同側(cè)下托部分區(qū)域葡萄糖代謝增加。術(shù)后第6天,雙側(cè)上丘,同側(cè)第一軀體感覺皮層、丘腦和后壓部皮層部分區(qū)域葡萄糖代謝增加。術(shù)后第9天,雙側(cè)丘腦、上丘、同側(cè)外側(cè)蒼白球和內(nèi)側(cè)膝狀體核以及小腦、延髓部分區(qū)域代謝增加。術(shù)后第15天,對側(cè)紋狀體、屏狀核、上丘和下丘部分區(qū)域代謝增加。術(shù)后第21天,雙側(cè)聽覺皮層,同側(cè)丘腦、下丘,以及小腦、中腦、延髓部分區(qū)域代謝增加?蹘Щ仄咸烟谴x在術(shù)后第1天和第9天降低。前額葉和海馬CA1區(qū)葡萄糖代謝在術(shù)后21天降低。羅哌卡因坐骨神經(jīng)阻滯下減弱術(shù)后島葉、尾狀殼核、海馬CA3區(qū)域、第一軀體感覺皮層、和丘腦等腦區(qū)葡萄糖代謝。結(jié)論:手術(shù)傷害性刺激上傳至大腦,引起疼痛矩陣和學(xué)習(xí)記憶相關(guān)腦區(qū)葡萄糖代謝發(fā)生改變,其中島葉、尾狀殼核、海馬CA3等腦區(qū)的激活。坐骨神經(jīng)阻滯可以有效地減輕術(shù)后早期疼痛,并減弱手術(shù)傷害刺激對島葉、尾狀殼核、海馬等腦區(qū)的激活。前言:圍術(shù)期藥物過敏反應(yīng)發(fā)生率可以高達(dá)1:385,一旦發(fā)生,病情變化迅速,可嚴(yán)重威脅患者生命安全。有研究報道表明,手術(shù)麻醉過程中藥物過敏導(dǎo)致3%至9.2%患者死亡。過敏反應(yīng)發(fā)生時,及時正確的處理和其后續(xù)的過敏原檢測十分重要?焖俜磻(yīng)及時治療有助于挽救患者生命。明確過敏藥物,可以幫助患者在之后的手術(shù)麻醉中避免使用該藥物,減少過敏反應(yīng)發(fā)生的風(fēng)險。尤其是在當(dāng)今社會,老齡化趨勢逐漸加重,人們接受手術(shù)治療的可能性也大大增加。在我們的研究中,既往發(fā)生圍術(shù)期局部麻醉或者全身麻醉下疑似藥物過敏反應(yīng),或者既往多種食物藥物嚴(yán)重過敏,需要在局部麻醉或者全身麻醉下檢查或手術(shù)治療而有發(fā)生圍術(shù)期過敏反應(yīng)風(fēng)險的患者入組,進(jìn)行皮內(nèi)試驗和/或嗜堿性粒細(xì)胞活化實驗,結(jié)合患者病史,對疑似發(fā)生過敏反應(yīng)者進(jìn)行鑒別診斷,一方面獲得國人圍術(shù)期藥物過敏反應(yīng)的流行病學(xué)情況,另一方面通過檢測過敏原,找到替代藥物,減少患者再次發(fā)生過敏反應(yīng)的風(fēng)險,幫助患者順利完成手術(shù)。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過程中出現(xiàn)疑似藥物過敏反應(yīng)癥狀或者由于自身過敏體質(zhì)的患者進(jìn)入試驗,進(jìn)行皮內(nèi)測試和(或)嗜堿性粒細(xì)胞活化實驗,尋找可能的過敏原。測試藥物的選擇依據(jù)麻醉單記錄中用到的麻醉藥物,同時選擇記錄單以外的同類藥物作為可能的替代藥物進(jìn)行檢測;颊甙l(fā)生反應(yīng)時的癥狀、發(fā)生反應(yīng)時間和使用藥物結(jié)合皮內(nèi)試驗和嗜堿性粒細(xì)胞活化實驗的結(jié)果用來判定圍術(shù)期藥物過敏反應(yīng)的存在及判定藥物過敏原。皮內(nèi)試驗使用0.9%生理鹽水作為陰性對照;使用10mg/ml組胺溶液作為陽性對照;待檢測藥物稀釋至1:1000(注:肌松藥及嗎啡為1:10000稀釋液)。在患者前臂、上臂或者后背注射0.02-0.03ml藥液,產(chǎn)生直徑約為3mm注射皮丘,15分鐘后記錄皮丘及紅暈的最大直徑和垂直直徑。陽性結(jié)果判斷標(biāo)準(zhǔn):注射部位周圍出現(xiàn)紅斑丘疹且伴有紅暈,風(fēng)團(tuán)直徑大于等于8mm,或者至少為注射直徑2倍。活化的嗜堿性粒細(xì)胞比例≥5%且刺激指數(shù)SI(SI=藥物活化的嗜堿性粒細(xì)胞比例/陰性質(zhì)控活化的嗜堿性粒細(xì)胞比例)≥2,作為藥物檢測的陽性標(biāo)準(zhǔn)。結(jié)果:在進(jìn)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靜脈麻醉下圍術(shù)期發(fā)生疑似過敏反應(yīng)而就診;42名患者由于既往局部麻醉下圍術(shù)期發(fā)生疑似過敏反應(yīng)而就診;15名患者既往未發(fā)生局部麻醉或全身麻醉不良反應(yīng),但是由于多種藥物食物嚴(yán)重過敏且有手術(shù)麻醉需求而要求進(jìn)行麻醉過敏原檢測。既往發(fā)生過疑似過敏反應(yīng)的81名患者中,一共有36名患者確診發(fā)生了藥物過敏反應(yīng),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靜脈麻醉過程中發(fā)生過敏反應(yīng),5名患者在局部麻醉下發(fā)生過敏反應(yīng),全身麻醉下發(fā)生的過敏反應(yīng)是局部麻醉下過敏反應(yīng)的6.2倍。全身麻醉下發(fā)生過敏反應(yīng)的31名患者,有2名患者分別發(fā)生2次過敏反應(yīng),因此共發(fā)生了33次圍術(shù)期過敏反應(yīng)。在全身麻醉下圍術(shù)期過敏反應(yīng)中,抗生素過敏者8例,肌松藥過敏者7例,咪達(dá)唑侖過敏者5例,異丙酚過敏者3例,依托咪酯過敏者1例,舒芬太尼過敏者3例,安定過敏者1例。利多卡因過敏者1例。琥珀酰明膠過敏者3例。局部麻醉藥物過敏的5人中,利多卡因過敏者3例,其中1例同時對阿替卡因過敏,羅哌卡因過敏者2例。共38名患者順利手術(shù),其中由于既往在全身麻醉下或者靜脈麻醉下圍術(shù)期發(fā)生疑似過敏反應(yīng)而就診的患者中,20名患者順利再次手術(shù);由于既往局部麻醉下圍術(shù)期發(fā)生疑似過敏反應(yīng)而就診的患者中,11名順利再次手術(shù);既往未發(fā)生局部麻醉或全身麻醉不良反應(yīng)而進(jìn)行麻醉藥物過敏原檢測的患者中,7名患者順利手術(shù)。結(jié)論:在圍術(shù)期過敏反應(yīng)中,女性患者多于男性,女性是男性的女性是男性的1.8倍。在全麻麻醉誘導(dǎo)的過敏反應(yīng)中,78.8%發(fā)生在誘導(dǎo)階段;91%出現(xiàn)了心血管癥狀;抗生素和肌松藥是最主要的過敏原。
[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.
【學(xué)位授予單位】:北京協(xié)和醫(yī)學(xué)院
【學(xué)位級別】:博士
【學(xué)位授予年份】:2016
【分類號】:R614
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