The Effect of Low-dose Katemine on Midazolam and Fentanyl Sedation and Analgesia
魏灵欣　硕士研究生　　邓晓明　教授　　刘慧丽　硕士研究生
张雁鸣　主治医师　　罗茂平　主治医师　　唐耿志　主治医师
刘建华　主治医师　　胥锟琳　教授<?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" />

中国医学科学院中国协和医科大学整形外科医院麻醉科，北京100041
Ling-xin Wei, Xiao-ming Deng, Hui-li Liu, Yan-ming Zhang, Mao-ping Luo, Geng-zhi Tang, Jian-hua Liu, Kun-lin Xu
Department of Anesthesiology, Plastic Surgery Hospital of Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100041

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ABSTRACT

　　Objective：To observe the clinical effect of low-dose ketamine on midazolam and fentanyl sedation/analgesia in plastic procedures with local anesthesia.
　　Methods：40 unpremedicated ASA classⅠpatients undergoing elective plastic surgery with local anesthesia and sedation were randomly divided into group M-F and group M-F-K . After placement of the intravenous catheter, all patients received bolus of midazolam 0.05mg•kg^-1, fentanyl 0.5μg•kg^-1 (Group M-F), and ketamine 0.3 mg•kg^-1 (Group M-F-K) iv, followed by a maintenance infusion at an initial rate of midazolam 0.1mg•kg^-1•h^-1 , fentanyl 1μg•kg^-1•h^-1(Group M-F), and ketamine 0.5 mg•kg^-1•h^-1 (Group M-F-K) respectively. The rate of infusion was decreased gradually according to the level of conscious sedation, and the infusion was discontinued at the end of procedure in both groups. Vital signs and sedative score (SS) were assessed continuously. Intraoperative and postoperative 24h side effects, such as hypoxia, apnea, nausea and vomiting were recorded.
　　Results：The total dosage of midazolam in group M-F and group M-F-K were 12.96±3.14mg and 11±3.29mg while fentanyl were 147.26±41.01μg and 132.79±46.33μg, respectively. The dose of katemine was 44.34±20.52mg in group M-F-K. Compared with group M-F, the incidence of injection pain caused by local anesthesia in M-F-K group is significantly decreased (20% versus 50%).In group M-F and group M-F-K, the incidence of respiratory depression were 25% and 20% respectively, and of PONV were 25% and 15% respectively.
　　Conclusions：The sedative techniques of both M-F and M-F-K are safe ly used in plastic procedures with local anesthesia. Whereas low-dose ketamine can significantly improve the sedative and analgesia effect of midazolam and fentanyl.
　　Key words：Sedation; Analgesia; Local anesthesia; Ketamine
　　Corresponding author: Xiao-ming Deng, MD

　　氯胺酮为传统静脉全麻药物，是一种非竞争性NMDA受体拮抗剂，具有良好的镇痛和分离麻醉的特点。近年来，有关小剂量氯胺酮的研究日渐深入，其镇痛作用得到了广泛的认可。临床仅使用麻醉浓度氯胺酮的1/5～1/10量，即可明显抑制NMDA 受体的活性，产生有效的镇痛作用^[1]。在整形外科局麻手术时，小剂量氯胺酮与咪达唑仑复合使用不仅能提高咪达唑仑的镇静遗忘作用，减少用量，还有良好的镇痛效果，可有效地减少注射局麻药时的疼痛反应^[2]。此外，临床和药理学的研究均证实^[3]，小剂量氯胺酮与阿片药物联合应用时，可产生协同作用，降低各自的不良反应，明显提高镇痛质量。本文观察小剂量氯胺酮对咪达唑仑复合芬太尼镇静镇痛的影响，为临床选择提供参考。

资料与方法<?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" />

一、病例选择
    在获得病人书面同意后，40例ASAⅠへⅡ级择期整形外科局麻手术病人随机分为两组，每组20例。M-F组应用咪达唑仑，芬太尼镇静，M-F-K组应用咪达唑仑，芬太尼和小剂量氯胺酮镇静。手术种类包括面、颈、四肢、躯干扩张器埋置、取出和瘢痕切除修复术，颜面部除皱术，唇裂继发畸形矫正术，鼻整形术及乳房硅胶假体置入术。有心、肺疾患，精神病史或智力障碍的患者、有安定阿片类药物服用史的患者除外。
二、麻醉方法
    患者术前禁食、禁水8 h，入室后建立静脉通道并测定血压（BP）、心率（HR）、脉搏血氧饱和度（SpO₂）、呼吸频率（RR）及镇静评分（SS）。静脉给予东莨菪碱（0.1-0.2mg）3 min后给予咪达唑仑0.05mg•kg^-1，芬太尼0.5mg•μg^-1（2-3 min内注入）。在注射局麻药前2-3 min，M-F 组静脉注入生理盐水2ml，M-F-K组给予稀释为2ml的氯胺酮0.3mg•kg^-1。然后用佳士比3100型输液泵连续输注由专人配制的咪达唑仑、芬太尼（M-F组）和氯胺酮（M-F-K组）的复合液，输注方案：根据镇静深度调整，前30分钟咪达唑仑、芬太尼或氯胺酮输注速度分别为：0.1mg•kg^-1•h^-1 、1μg•kg^-1•h^-1和0.5mg•kg^-1•h^-1，30-120分钟输注速度分别为0.08mg•kg^-1•h^-1 、0.08 μg•kg^-1•h^-1和 0.4mg•kg^-1•h^-1，120分钟以后分别为0.06mg•kg^-1•h^-1、0.06μg•kg^-1•h^-1和0.3mg•kg^-1•h^-1。手术缝合结束时停止药物输注。
    手术区域用含1 : 400，000肾上腺素的0.5％的利多卡因和/或0.25％利多卡因局部侵润，手术时间超过60 min者混合加用0.125％罗哌卡因。
    术中常规吸入空气，当SpO₂<90％，持续时间超过10秒时暂停药物输注，必要时鼻导管或面罩供氧。当SpO₂>95％后恢复药物输注，输注速度减慢1个梯度。
三、监测与观察项目
    术中用惠普监测仪每隔5min监测BP、HR，连续监测SpO₂和心电图（ECG）。分别在给药前、给药后3min、给药后5min、注射局麻药时、手术切皮、停药时、停药后10min及出手术室时记录SpO₂、HR、BP、RR及SS。SS采用White镇静评分法^[3]（1=清醒/紧张，2=清醒/放松，3=清醒/嗜睡，4=睡眠/易唤醒，5=睡眠/难唤醒，6=语言不能唤醒）。1-2分为镇静不充分，3-4分为镇静合适，5-6分为镇静过深。
　　术中观察记录病人是否有低氧血症（SpO₂<90％，持续时间大于10秒），呼吸暂停（无呼吸时间大于15秒），是否需要呼吸提示、吸氧或辅助呼吸，是否有躁动、谵语、呃逆或恶心呕吐。记录病人停药后复述生日、恢复定向力的时间。术后病人清醒，呼吸循环稳定，定向力恢复并能复述生日后直接送返病房。术后24 h随访，记录病人恶心呕吐、噩梦、视力模糊，术中记忆的发生情况并调查病人对麻醉的满意度以及今后类似手术是否愿意选择同样的麻醉方法。
　　统计学处理: 所有计量资料以均数±标准差（±s）表示，用SPSS11.0统计软件进行统计分析。组间计量资料作两个独立样本的t检验，两组的镇静评分作两个独立样本的秩和检验。两组间率的比较采用卡方检验。P<0.05表示有统计学差异。

　　在本观察中，两组均有部分病例出现一过性的低氧血症，多数在静脉注射芬太尼后出现，经呼吸提示后能迅速缓解。提示在使用镇静镇痛时，必须加强呼吸道的管理，常规吸氧。本观察常规吸入空气，是为了便于观察和比较两种用药方式对呼吸功能的影响。
　　本研究采用单次给药后连续输注技术。与传统的间断分次给药技术相比，连续输注技术不仅可以减少药物用量，还能避免血药浓度的上下波动，使术中的镇静水平相对平稳；停药后血药浓度又能快速下降，缩短恢复时间。在本观察中，两组病人对注射局部麻醉药和主要手术操作引起的不适和疼痛均无记忆，停药后均快速恢复。尽管病人的应答能力以及定向力恢复较快，但记忆功能的恢复仍须较长时间。
　　恶心呕吐是镇静镇痛的主要并发症之一，不仅影响患者术后恢复的质量，术中还可能污染术野，甚至出现误吸。通常情况下，咪达唑仑复合量氯胺酮镇静时呕吐的发生率仅为2％～ 9.6％^[10，11]。而本观察中两组病人术后恶心呕吐发生率较高，分别15％和25％，可能与芬太尼有关。
　　小结：M-F 组和M-F-K组均可安全有效地用于整形外科局部麻醉手术，以M-F-K组的镇痛效果更加理想。<?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" />

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