【作者】 吉阳；

【导师】 罗朝志；

【作者基本信息】 四川大学 ， 麻醉学， 2007， 硕士

【摘要】 目的：观察不同配伍剂量的咪唑安定+芬太尼用于局部麻醉镇静，在达到相同镇静程度时镇静效果和副作用的发生情况，比较哪种药物组合能较快获得最佳的镇静效果，并且副作用较少，以确定这两种药物的最佳组合，为临床使用这种镇静方法提供依据和参考。方法：本实验为多中心、随机、双盲、前瞻性实验，由5个中心共同完成，每个中心完成60例。300例行局部麻醉的病人，体重40-80kg、年龄18-70岁、无明显心、肺、肝、肾疾病，根据使用咪唑安定+芬太尼的配方的不同随机分为5组，每组60例。M+F₁₀₀组：咪唑安定10mg+芬太尼100μg；M+F₂₀₀组：咪唑安定10mg+芬太尼200μg；M+F₃₀₀组：咪唑安定10mg+芬太尼300μg；M+F₄₀₀组：咪唑安定10mg+芬太尼400μg：M+F₅₀₀组：咪唑安定10mg+芬太尼500μg。为保证盲法的实施，以上各组药物配方均用生理盐水稀释到20ml。采用小剂量分次给药（每次2ml，隔5分钟后追加2ml）的方法使各组病人达到改良Wilson镇静分级2级，观察并记录实验期内各组病人镇静药用量、达镇静级别所用的时间、呼吸循环功能变化及相关并发症的发生率、术中遗忘率和麻醉医师对镇静质量的总体评价（VAS评分）等情况，用SPSS统计软件进行统计学比较，确定咪唑安定+芬太尼的最佳配伍方法。结果：1．各组病人一般情况无统计学差异，组间具有可比性。2．M+F₁₀₀组病人镇静达2级所用的时间最长为19．1±7．0min，M+F₅₀₀组病人镇静达2级所用的时间最短为13．0±6．1min；M+F₂₀₀组、M+F₃₀₀和M+F₄₀₀组病人镇静达2级所用的时间分别为17．8±7．9min、16．2±7．0min和14．2±6．0min。3．M+F₃₀₀组病人镇静质量的VAS评分最高为9．2±0．7，与M+F₁₀₀组、M+F₄₀₀组和M+F₅₀₀组比较有统计学差异；M+F₂₀₀组镇静质量的VAS评分为8．9±0．7，与M+F₃₀₀组比较无统计学差异；M+F₁₀₀组、M+F₄₀₀组和M+F₅₀₀组镇静质量的VAS评分较低，分别为7．8±1．5、8．4±1．4和8．3±1．2。4．各组病人术中遗忘率均较高，平均为70％，组间比较无统计学差异。5．各组病人的血流动力学变化轻微，组间变化无统计学差异，在达到改良Wilson镇静分级2级时，无明显的循环抑制发生。6．随着镇静配方中芬太尼用量的加大，药物对呼吸功能的影响趋于加重，呼吸并发症增加。M+F₁₀₀组病人芬太尼的用量最少为38．8±13．4μg，呼吸并发症最少：RR＜8次／min的发生率为3.3％、SpO₂＜95％的发生率为21．7％、SPO₂＜90％发生率为0、中重度呼吸道梗阻发生率为3．3％；M+F₄₀₀组和M+F₅₀₀组病人芬太尼用量较大，分别为117．3±47．0μg和140．0±57．3μg，对呼吸的影响严重，呼吸并发症多：RR＜8次／min的发生率分别为20％和30％、SpO₂＜95％的发生率分别为38．3％和50．0％、SPO₂＜90％的发生率分别为25．0％和33．3％、中重度呼吸道梗阻发生率分别为10．0％和28．3％；M+F₂₀₀组和M+F₃₀₀组芬太尼用量较少分别为66．3±31．9μg和99．6±39．1μg，呼吸并发症相对较少：RR＜8次／min的发生率分别为6．7％和11．7％、SpO₂＜95％的发生率分别为25．0％和33．3％、SPO₂＜90％的发生率两组均为11．7％、中重度呼吸道梗阻发生率两组均为8．3％。结论：采用M+F₂₀₀组和M+F₃₀₀组配方，用小剂量分次给药的方法对局部麻醉病人进行镇静，能较快达到改良Wilson镇静分级2级，并且镇静质量较高、遗忘效果好、对循环功能无明显抑制，呼吸抑制相对较轻、呼吸并发症较少，是理想的咪唑安定和芬太尼配伍方法。更多还原

【Abstract】 Objective: To investigate the efficacy and respiratory complications of midazolam combined with different dose fentanyl for sedation during regional anesthesia, and to determine the appropriate dosage regimen.Methods: Three hundred patients undergoing surgery with regional anesthesia were enrolled in this multicenter, double-blind, randomized study. Patients were randomly assigned to five groups of 60 patients each according to the dosage of midazolam and fentanyl in a bolus. (groupM+F₁₀₀: midazolam 1mg/ fentanyl 10μg; groupM+F₂₀₀: midazolam 1mg/ fentanyl 20μg; groupM+F₃₀₀: midazolam 1mg/ fentanyl 30μg; groupM+F₄₀₀: midazolam 1mg/ fentanyl 40μg; groupM+F₅₀₀: midazolam 1mg/ fentanyl 50μg).Patients received 2 ml mixture （a bolus） of midazolam and fentanyl every 5min until a Modified Wilson Sedation Scale of 2 was achieved. BP,HR,RR,SpO₂,and PetCO₂ were measured every 5min for 45min. Intraoperative amnesia effects was assessed using picture recall test. The time required to achieve Modified Wilson sedation scale of 2, total dose of midazolam and fentanyl, and perioperative complications were recorded. The investigator’s overall satisfaction with the sedation protocol was assessed using the visual analog scale （VAS）. Data was analyzed using SPSS program.Results: The groups were comparable in terms of sex, age, height and weight. The time to achieve Modified Wilson sedation scale score of 2 in groupM+F₁₀₀, groupM+F₂₀₀, groupM+F₃₀₀, groupM+F₄₀₀, and groupM+F₅₀₀ were 19.1±7.0min, 17.8±7.9min, 16.2±7.0min, 14.2±6.0min, and 13.0±6.1 min, respectively. The overall amnesia effects among 5 groups was 70.0%, there were no significant differences in the amnesia effects between 5 groups. The investigator’s overall satisfaction with the sedation protocol in groupM+F₃₀₀ was 9.2±0.7 which was significantly higher than that in groupM+F₁₀₀, groupM+F₄₀₀,and groupM+F₅₀₀, there were no significant differences in the investigator’s overall satisfaction with the sedation protocol between groupM+F₂₀₀ and groupM+F₃₀₀（8.9±0.7）. Each group had a stable hemodynamics, there were no significant differences in the hemodynamic variables between 5 groups. With increasing the doses of fentanyl, respiratory complications progressively increased. Patients in groupM+F₁₀₀ received smaller doses fentanyl （38.8±13.4μg）, resulted in fewer respiratory complications: 3.3% patients experienced bradypnea （＜8 breaths/min）, 21.7% patients experienced moderate oxygen desaturation （SpO₂＜95%）, and 3.3% patients experienced upper respiratory obstruction. Respiratory complications occurred more often in group M+F₄₀₀ and group M+F500 due to their relatively more fentanyl doses （117.3±41.7μg and 140.0±57.3μg, respectively）,23.3% patients in group M+F₄₀₀ and 35.0% patients in group M+F₅₀₀ experienced severe oxygen desaturation （SpO₂＜90%）, 38.3% patients in group M+F₄₀₀ and 50.0% patients in group M+F₅₀₀ experienced moderate oxygen desaturation （SpO₂＜95%）, 20.0% patients in group M+F₄₀₀ and 30.0% patients in group M+F₅₀₀ experienced bradypnea （＜8 breaths/min）, 10.0% patients in group M+F₄₀₀ and 28.3% patients in group M+F₅₀₀ experienced upper respiratory obstruction. A moderate dose of fentanyl （66.3±31.9μg and 99.6±39.1μg） was administered to the patients in group M+F₂₀₀ and groupM+F₃₀₀ respectively.25.0% patients in group M+F₂₀₀ and 33.3% patients in group M+F₃₀₀ experienced moderate oxygen desaturation (（SpO₂＜95%）,11.7% patients and 8.3% patients in both groups experienced severe oxygen desaturation (（SpO₂＜90%） and upper airway obstruction, respectively; 6.7% patients in group M+F₂₀₀ and 11.7% patients in group M+F₃₀₀ experienced bradypnea （＜8 breaths/min）.Conclusion: Intravenous sedation with intermittent midazolam 1mg combined with fentany 20μg or 30ug was a safe and effective dosage regimen for regional anesthesia, provided adequate sedation and amnesia with a stable hemodynamics, and resulted in fewer respiratory complications.更多还原