發(fā)布時間：2018-04-28 09:35

  本文選題：組胺H_1拮抗劑 + 圍手術(shù)期　； 參考：《山東大學》2017年碩士論文

【摘要】：背景及目的:圍手術(shù)期有很多因素可激發(fā)組胺釋放,其涵蓋了藥品、乳膠、血及血制品等物質(zhì)的作用。輕者僅有皮膚反應,重者可致嚴重的呼吸循環(huán)紊亂危及生命。因此,有效地防治圍手術(shù)期藥物誘發(fā)的組胺釋放十分必要。富馬酸氯馬斯汀是一種新型H1受體拮抗劑,起效快、抗組胺作用強、效果持續(xù)時間長,有良好的抗組胺效應。對過敏原誘發(fā)的組胺釋放,富馬酸氯馬斯汀不僅在H1受體水平拮抗組胺,而且還能對肥大細胞發(fā)揮抑制組胺釋放的功能,可發(fā)揮良好的抗組胺效果。本研究選取了圍手術(shù)期常用且較易誘發(fā)組胺釋放兩種藥物:阿曲庫銨和魚精蛋白,擬評價富馬酸氯馬斯汀注射液對上述兩種藥物于圍手術(shù)期藥物誘發(fā)組胺釋放的防治效果。方法:臨床研究一:擇期行乳腺癌改良根治術(shù)患者80例,年齡20-60歲,BMI 17～26 kg/m2,ASA分級Ⅰ或Ⅱ級。通過隨機數(shù)字表法,將研究對象劃歸為2組(n=40):對照組(C組)和富馬酸氯馬斯汀組(CF組),CF組于麻醉誘導前20 min肌肉注射富馬酸氯馬斯汀2 mg。依次靜脈注射咪達唑侖0.1mg/kg、依托咪酯0.3mg/kg、芬太尼4-6μg/kg和阿曲庫銨0.8 mg/kg麻醉誘導后置入喉罩,行機械通氣,吸入2%七氟醚維持麻醉。分別于富馬酸氯馬斯汀給藥前(T0)、給藥后20min(T1)、阿曲庫銨給藥前即刻(T2)、給藥后2、5、10、20min(T3～6)時記錄患者的血壓和心率,并采集動脈血樣,測定血漿組胺濃度,記錄氣道峰壓和局部皮膚顏色程度,評估高組胺血癥和心血管事件發(fā)生情況;拔除喉罩后10 min時記錄Steward蘇醒評分與Ramsay鎮(zhèn)靜評分。臨床研究二:選擇山東大學齊魯醫(yī)院準備進行擇期非體外循環(huán)冠狀動脈移植術(shù)(OP-CABG)病人60例,并隨機將病人均分為兩組:生理鹽水對照組(C組)和組胺H1受體拮抗藥富馬酸氯馬斯汀組(CF組)。CF組于魚精蛋白中和肝素前20分鐘肌肉注射富馬酸氯馬斯汀注射液2mg(2ml);C組給予等容量生理鹽水。分別于魚精蛋白中和肝素前0.5分鐘(T0)、魚精蛋白中和肝素后2分鐘(T1)、5分鐘(T2)、10分鐘(T3)、20分鐘(T4)、30分鐘(T5)觀測患者的心率(HR)、收縮壓(SP)、舒張壓(DP)、平均動脈壓(MAP)和中心靜脈壓(CVP),并在相應的觀測時間點取動脈血檢測血漿組胺濃度。記錄術(shù)中魚精蛋白中和肝素時魚精蛋白靜注用時、靜注停頓次數(shù)以及給予魚精蛋白后30分鐘內(nèi)血管活性藥物使用情況。結(jié)果:臨床研究一:C組和CF組給予阿曲庫銨后高組胺血癥發(fā)生率分別為60%和8%;與C組比較,CF組T3～5時血漿組胺濃度和給予阿曲庫銨后高組胺血癥發(fā)生率降低(P0.05或0.01)。與C組比較,CF組低血壓和心動過速的發(fā)生率及間羥胺和艾司洛爾的使用劑量降低(P0.05)。與C組比較,CF組局部皮膚顏色程度降低(P0.05);2組之間及組內(nèi)氣道峰壓比較差異不具有統(tǒng)計學意義(P0.05)。2組患者Steward蘇醒評分與Ramsay鎮(zhèn)靜評分差異無統(tǒng)計學意義(P0.05)。臨床研究二:與C組比較,CF組在T1時HR減慢,T1,2時SP、DP、MAP和CVP升高(P0.05或0.01);靜注魚精蛋白的用時明顯縮短,靜注停頓次數(shù)和去甲腎上腺素使用量明顯減少(P0.01);CF組在T1～T3時血漿組胺濃度明顯降低(P0.05 或 0.01)。結(jié)論:臨床研究一:對于阿曲庫銨誘發(fā)全麻手術(shù)患者的組胺釋放,術(shù)前肌肉注射富馬酸氯馬斯汀2mg,不僅可在H1受體水平拮抗組胺,還可減少組胺釋放量,可產(chǎn)生良好的抗組胺效應;富馬酸氯馬斯汀對患者麻醉恢復程度未產(chǎn)生明顯影響,不干擾麻醉恢復。臨床研究二:對于OP-CABG全麻手術(shù)患者,魚精蛋白中和肝素前肌肉注射富馬酸氯馬斯汀2mg,能夠有效抑制靜注魚精蛋白所引起的循環(huán)功能波動,可產(chǎn)生良好的抗組胺效應。
[Abstract]:Background and purpose: there are many factors that can stimulate histamine release during the perioperative period. It covers the effects of substances such as drugs, latex, blood and blood products. The light is the only skin reaction, and the severe respiratory and circulatory disorder endangers life. Therefore, it is necessary to effectively prevent and control the release of histamine induced by the peri operative drug. The fumaric acid chloride Mastin It is a new type of H1 receptor antagonist, which has fast effect, strong anti histamine effect, long lasting effect and good antihistamine effect. The release of histamine induced by allergen. Chlormalastine fumarate not only antagonize histamine at the level of H1 receptor, but also can inhibit histamine release from mast cells, and can play a good antihistamine effect. In this study, two kinds of drugs commonly used in perioperative period and easy to induce histamine release were selected: atracurium and protamine. The effect of chloramastine fumarate injection on the release of histamine induced histamine induced by the two kinds of drugs in perioperative period was evaluated. Method: clinical study 1: 80 patients with modified radical mastectomy for breast cancer, age 20-60, and age 20-60. Age, BMI 17~26 kg/m2, ASA grade I or class II. The subjects were classified into 2 groups (n=40) by random numbers: control group (C group) and fumarine fumarine group (CF group), CF group was injected 20 min muscle of fumaric acid with midazolam 0.1mg/kg, etomidate 0.3mg/kg, fentanyl 4-6 micron before induction of anesthesia induction. And atracurium 0.8 mg/kg anesthesia induction after the induction of laryngeal mask, mechanical ventilation, inhaled 2% sevoflurane anesthesia. Before the fumarate chloride Mastin Administration (T0), 20min (T1) after administration, atracurium was given immediately before administration (T2), after 2,5,10,20min (T3 to 6), recorded the patient's blood pressure and heart rate, and collect arterial blood samples, determination of histamine concentration in plasma. Degree, the peak pressure of the airway and the degree of local skin color, the evaluation of hyperhistamine and the occurrence of cardiovascular events; the Steward awakening score and the Ramsay sedation score were recorded at 10 min after the extraction of the larynx. Clinical study two: 60 cases of elective non cardiopulmonary bypass coronary artery transplantation (OP-CABG) were selected in Qilu Hospital of Shandong University, and The patients were randomly divided into two groups: normal saline control group (group C) and histamine H1 receptor antagonist (group CF), group.CF was injected with 2mg (2ml) with chloramine fumarate injection for 20 minutes before and after protamine and heparin; C group was given equal volume physiological salt water. 0.5 minutes before protamine neutralized heparin (T0) and protamine, respectively. The protein and heparin were 2 minutes (T1), 5 minutes (T2), 10 minutes (T3), 20 minutes (T4), and 30 minutes (T5) to observe the patients' heart rate (HR), systolic pressure (SP), diastolic pressure (DP), mean arterial pressure (MAP) and central venous pressure (CVP), and the blood plasma histamine concentration was detected by arterial blood at the corresponding time point. Protamine and heparin were recorded during the operation. The number of static annotation and the use of vasoactive drugs within 30 minutes after protamine were used. Results: clinical study 1: the incidence of hyperhistamine after atracurium in group C and group CF was 60% and 8%, respectively. Compared with group C, the plasma histamine concentration and the incidence of hyperhistamines after atracurium were lower in group CF (T3 ~ 5). P0.05 or 0.01). Compared with group C, the incidence of hypotension and tachycardia in group CF and the use of hydroxylamine and Ai Si lol decreased (P0.05). Compared with the C group, the local skin color degree of CF group decreased (P0.05), and the difference between the 2 groups and the internal airway peak pressure was not significant (P0.05) the Steward awakening score and the Ramsay town of the.2 group. There was no significant difference in static score (P0.05). Clinical study two: compared with group C, group CF slowed down at T1, SP, DP, MAP and CVP increased (P0.05 or 0.01) when T1,2, and the use of protamine was obviously shortened, and the number of static injection pause and the use of norepinephrine decreased significantly (P0.01). Or 0.01) conclusion: clinical study 1: for the histamine release of patients with atracurium induced general anesthesia, intramuscular injection of fumaric acid chloride Mastin 2mg before operation not only can antagonize histamine at the level of H1 receptor, but also reduce histamine release and produce a good antihistamine effect. Effect, do not interfere with the recovery of anesthesia. Clinical study two: for the patients with OP-CABG general anesthesia, protamine and heparin injection of fumaric acid chloride Mastin 2mg before and before heparin can effectively inhibit the circulation function fluctuations caused by the intravenous protamine, and produce good antihistamine effect.

【學位授予單位】：山東大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R614

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