富马酸氯马斯汀注射液用于围手术期药物诱发组胺释放的防治效果

发布时间：2018-04-28 09:35

本文选题：组胺H_1拮抗剂 + 围手术期　；参考：《山东大学》2017年硕士论文

【摘要】：背景及目的:围手术期有很多因素可激发组胺释放,其涵盖了药品、乳胶、血及血制品等物质的作用。轻者仅有皮肤反应,重者可致严重的呼吸循环紊乱危及生命。因此,有效地防治围手术期药物诱发的组胺释放十分必要。富马酸氯马斯汀是一种新型H1受体拮抗剂,起效快、抗组胺作用强、效果持续时间长,有良好的抗组胺效应。对过敏原诱发的组胺释放,富马酸氯马斯汀不仅在H1受体水平拮抗组胺,而且还能对肥大细胞发挥抑制组胺释放的功能,可发挥良好的抗组胺效果。本研究选取了围手术期常用且较易诱发组胺释放两种药物:阿曲库铵和鱼精蛋白,拟评价富马酸氯马斯汀注射液对上述两种药物于围手术期药物诱发组胺释放的防治效果。方法:临床研究一:择期行乳腺癌改良根治术患者80例,年龄20-60岁,BMI 17～26 kg/m2,ASA分级Ⅰ或Ⅱ级。通过随机数字表法,将研究对象划归为2组(n=40):对照组(C组)和富马酸氯马斯汀组(CF组),CF组于麻醉诱导前20 min肌肉注射富马酸氯马斯汀2 mg。依次静脉注射咪达唑仑0.1mg/kg、依托咪酯0.3mg/kg、芬太尼4-6μg/kg和阿曲库铵0.8 mg/kg麻醉诱导后置入喉罩,行机械通气,吸入2%七氟醚维持麻醉。分别于富马酸氯马斯汀给药前(T0)、给药后20min(T1)、阿曲库铵给药前即刻(T2)、给药后2、5、10、20min(T3～6)时记录患者的血压和心率,并采集动脉血样,测定血浆组胺浓度,记录气道峰压和局部皮肤颜色程度,评估高组胺血症和心血管事件发生情况;拔除喉罩后10 min时记录Steward苏醒评分与Ramsay镇静评分。临床研究二:选择山东大学齐鲁医院准备进行择期非体外循环冠状动脉移植术(OP-CABG)病人60例,并随机将病人均分为两组:生理盐水对照组(C组)和组胺H1受体拮抗药富马酸氯马斯汀组(CF组)。CF组于鱼精蛋白中和肝素前20分钟肌肉注射富马酸氯马斯汀注射液2mg(2ml);C组给予等容量生理盐水。分别于鱼精蛋白中和肝素前0.5分钟(T0)、鱼精蛋白中和肝素后2分钟(T1)、5分钟(T2)、10分钟(T3)、20分钟(T4)、30分钟(T5)观测患者的心率(HR)、收缩压(SP)、舒张压(DP)、平均动脉压(MAP)和中心静脉压(CVP),并在相应的观测时间点取动脉血检测血浆组胺浓度。记录术中鱼精蛋白中和肝素时鱼精蛋白静注用时、静注停顿次数以及给予鱼精蛋白后30分钟内血管活性药物使用情况。结果:临床研究一:C组和CF组给予阿曲库铵后高组胺血症发生率分别为60%和8%;与C组比较,CF组T3～5时血浆组胺浓度和给予阿曲库铵后高组胺血症发生率降低(P0.05或0.01)。与C组比较,CF组低血压和心动过速的发生率及间羟胺和艾司洛尔的使用剂量降低(P0.05)。与C组比较,CF组局部皮肤颜色程度降低(P0.05);2组之间及组内气道峰压比较差异不具有统计学意义(P0.05)。2组患者Steward苏醒评分与Ramsay镇静评分差异无统计学意义(P0.05)。临床研究二:与C组比较,CF组在T1时HR减慢,T1,2时SP、DP、MAP和CVP升高(P0.05或0.01);静注鱼精蛋白的用时明显缩短,静注停顿次数和去甲肾上腺素使用量明显减少(P0.01);CF组在T1～T3时血浆组胺浓度明显降低(P0.05 或 0.01)。结论:临床研究一:对于阿曲库铵诱发全麻手术患者的组胺释放,术前肌肉注射富马酸氯马斯汀2mg,不仅可在H1受体水平拮抗组胺,还可减少组胺释放量,可产生良好的抗组胺效应;富马酸氯马斯汀对患者麻醉恢复程度未产生明显影响,不干扰麻醉恢复。临床研究二:对于OP-CABG全麻手术患者,鱼精蛋白中和肝素前肌肉注射富马酸氯马斯汀2mg,能够有效抑制静注鱼精蛋白所引起的循环功能波动,可产生良好的抗组胺效应。
[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.

【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R614

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