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1242 Chin JMAP,2013 November,Vol.30 No.11 中国现代应用药学 2013 年 11 月第 30 卷第 11 期 32(3):728-735.4 NELSON L E,GUO T Z,LU J,et al.The sedative component of anesthesia is mediated by GABA(A)receptors in an endogenous sleep pathway J.Nat Neurosci,2002,5(10):979-984.5 LYDIC R,BIEBUYCK J F.Sleep neurobiology:relevance for mechanistic studies of anaesthesia J.Br J Anaesth,1994,72(5):506-508.6 ALKIRE M T,POMFRETT C J,HAIER R J,et al.Functional brain imaging during anesthesia in humans:effects of halothane on global and regional cerebral glucose metabolism J.Anesthesiology,1999,90(3):701-709.7 SATO Y,SEO N,KOBAHASHI E.The dosing-time dependent effects of intravenous hypnotics in mice J.Anesth Analg,2005,101(6):1706-1708.8 CHEN W H,LI L Z,LIN P D,et al.Effect of remifentanil preconditioning in different concentrations on hepatic hypoxia-reoxygenation injury J.Chin J Mod Appl Pharm(中国现代应用药学),2013,30(2):125-130.9 HIRAO J,ARAKAWA S,WATANABE K,et al.Effects of restricted feeding on daily fluctuations of hepatic functions including p450 monooxygenase activities in rats J.J Biol Chem,2006,281(6):3165-3171.10 LI Y,LIU Z,ZHANG J,et al.Synchronisation mechanisms of circadian rhythms in the suprachiasmatic nucleus J.IET Syst Biol,2009,3(2):100-112.11 ALBUS H,VANSTEENSEL M J,MICHEL S,et al.A GABAergic mechanism is necessary for coupling dissociable ventral and dorsal regional oscillators within the circadian clock J.Curr Biol,2005,15(10):886-893.12 GOMPF H S,ALLEN C N.GABAergic synapses of the suprachiasmatic nucleus exhibit a diurnal rhythm of short-term synaptic plasticity J.Eur J Neurosci,2004,19(10):2791-2798.13 BONIN R P,ORSER B A.GABA(A)receptor subtypes underlying general anesthesia J.Pharmacol Biochem Behav,2008,90(1):105-112.收稿日期:2013-03-20 帕瑞昔布钠在甲状腺癌功能性颈淋巴结清扫术后镇痛效果的观察 彭友,罗定存*,张卧,潘钢,丁金旺(杭州市第一人民医院,杭州 310006)摘要:目的 研究帕瑞昔布钠对甲状腺癌功能性颈淋巴结清扫术患者术后镇痛效果和心理状态的影响。方法 根据美国麻醉师协会(ASA)分级,选择 ASA I-II 级择期全麻下行甲状腺癌功能性颈淋巴结清扫术患者 34 例,随机分为帕瑞昔布钠组和对照组。帕瑞昔布钠组于术毕即刻、术后 12,24,36 h 分别静脉注射帕瑞昔布钠 40 mg;对照组在各时点给予生理盐水 5 mL。分别于术后 6,12,24,48 h 记录视觉模拟镇痛评分(visualanaloguescale,VAS);并利用心理学自评量表对手术前后心理状态进行评价。结果 帕瑞昔布钠组 VAS 于术后 6,12,24 h 明显低于对照组(P0.05);帕瑞昔布钠组术后各项心理学评估指标均明显优于对照组(P0.05)。结论 术后应用帕瑞昔布钠镇痛效果良好,并可改善甲状腺癌功能性颈淋巴结清扫术患者术后心理应激状态。关键词:甲状腺肿瘤;颈淋巴结清扫术;帕瑞昔布钠;镇痛 中图分类号:R969.4 文献标志码:A 文章编号:1007-7693(2013)11-1242-03 Postoperative Analgesic Effect of Parecoxib in Thyroid Cancer Functional Neck Lymph Node Dissection PENG You,LUO Dingcun*,ZHANG Wo,PAN Gang,DING Jinwang(The First Peoples Hospital of Hangzhou,Hangzhou 310006,China)ABSTRACT:OBJECTIVE To study parecoxib thyroid cancer functional neck lymph node dissection in patients with postoperative analgesic effects and psychological state.METHODS According to the American Society of Anesthesiologists(ASA)classification,ASA I-II level elective anesthesia thyroid cancer,the functional cervical lymph node dissection in 34 patients were randomly divided into parecoxib sodium group and control group.Parecoxib group after operation immediately,12,24,36,respectively was intravenously given parecoxib sodium 40 mg;5 mL saline was administered at each time point in control group.After 6,12,24 and 48 h,mental state of the visual analog pain score(VAS)was recorded.The psychology self-rating scale before and after surgery were evaluated.RESULTS The parecoxib group VAS in postoperative 6,12,24 h,were significantly lower than the control group(P0.05);parecoxib sodium group after the psychology assessment indicators were significantly better than the control group(P0.05 0.05 0.05 0.05 1.2 麻醉方法 两组均采用气管内插管全身麻醉。依次静脉注射咪达唑仑0.020.04 mgkg1、芬太尼35 gkg1、丙泊酚1.52 mgkg1和维库溴铵0.1 mgkg1麻醉诱导,插入气管导管后接麻醉机行呼吸控制。术中维持麻醉,采用持续静脉泵入丙泊酚46 mgkg1h1和瑞芬太尼0.11.0 gkg1min1,同时吸入低浓度异氟醚(1.0%1.5%),并间断静脉注入维库溴铵维持麻醉。PAR组术毕拔管前5 min、术后12,24,36 h分别静脉注射帕瑞昔布钠40 mg(生理盐水稀释至5 mL,4 min内静脉注入),CON组给予等量生理盐水。1.3 指标观察与评价 患者于术后6,12,24,48 h进行疼痛程度评分,采用视觉模拟评分法(visualanaloguescale,VAS)。手术前后心理状态评价:焦虑状态采用状态-特质焦虑问卷评定,抑郁水平采用抑郁自评量表评价,恐惧采用恐惧症自评量表检测。1.4 统计学分析 采用SPSS15.0软件进行数据处理和统计分析。计量资料用(sx)表示,两组比较采用 t 检验,计数资料采用2检验。以P0.05为差异有统计学意义。2 结果 2.1 两组术后镇痛效果比较 PAR组术后6,12,24 h的VAS评分显著低于CON组,差异有统计学意义(P0.05),结果见表2。表 2 PAR 组和 CON 组术后 VAS 评分(sx)Tab 2 PAR and CON postoperative VAS scores(sx)术后 6 h 术后 12 h 术后 24 h 术后 48 hPAR 组 3.70.4 2.00.3 1.50.2 1.20.5 CON 组 4.20.5 2.30.4 1.70.3 1.30.4 t 值 3.220 2.474 2.287 0.664 P 值 0.005 0.05 0.05 2.2 两组心理状态比较 两组患者术前的焦虑、抑郁、恐惧评分差异无统计学意义(P0.05)。术后两组患者抑郁和恐惧评分均降低,PAR组患者焦虑、抑郁和恐惧评分均显著低于对照组(P0.05),结果见表3。表 3 两组患者手术前后焦虑、抑郁和恐惧评分(sx)Tab 3 Scores of anxiety,depression and fear of groups patients before and after surgical operation(sx)焦 虑 抑 郁 恐 惧 手术前手术后手术前 手术后 手术前 手术后PAR 组 34.63.524.62.560.52.7 52.52.2 14.71.56.71.3CON 组 33.93.328.32.659.23.1 55.12.3 13.91.78.21.5t 值 0.6004.2291.304 3.368 1.4553.116 P 值0.5530.0010.201 0.005 0.1550.005 3 讨论 近年来我国甲状腺癌的发病率呈现增高的趋势,甲状腺癌颈淋巴结清扫的手术率也随之增高,手术切口、术后伤口疼痛引起的伤害性刺激可使外 1244 Chin JMAP,2013 November,Vol.30 No.11 中国现代应用药学 2013 年 11 月第 30 卷第 11 期 周和中枢神经系统呈高敏感状态而产生应激反应,不利于患者的康复和术后转归1,随着镇痛药和镇痛技术的不断发展,术后镇痛技术日趋完善,使患者的满意度和生活质量亦随之得到明显提高2。术后镇痛可以防止外周神经和中枢神经系统敏感化,以减少围术期应激反应,改善患者的术后转归,具有重要的社会意义。术后疼痛从性质上而言,是手术后即刻发生的急性伤害性疼痛,通常持续不超过7 d3。手术创伤在导致疼痛的同时,还会引起心血管系统、呼吸系统、消化系统、泌尿系统、内分泌系统和代谢的改变,导致免疫力下降,产生精神心理改变4。这样术后镇痛显得格外重要。对乙酰氨基酚和NSAIDS或选择性COX-2抑制剂(帕瑞昔布钠)以及阿片类药物、曲马多等,是术后镇痛尤其是制止中、重度疼痛的最常用药物5。其中,帕瑞昔布钠是一种注射用高选择性环氧化酶-2(COX-2)抑制剂,具有外周和中枢双重镇痛作用,被广泛用于外科手术的超前镇痛和术后镇痛。帕瑞昔布钠为水溶性药物,吸收快,713 min出现可感知的止痛作用,且镇痛持久,止痛时间612 h,甚至更长。COX-2主要作用部位在脑组织内,帕瑞昔布钠经过体内酶水解后完全转化为伐地昔布,伐地昔布是高选择性COX-2抑制剂,镇痛效果确切,且镇痛时间长6。伐地昔布通过抑制炎性介质和致痛物质的释放,降低周围性痛觉过敏,减少伤害性刺激传入脊髓后角神经元。同时抑制脊髓背角和大脑皮层COX-2,可有效抑制手术刺激诱发的心血管反应,降低术后VAS评分,而对术毕苏醒时间无影响。吴震等7发现静脉内预先给帕瑞昔布钠能显著提高布托啡诺术后镇痛效果,减少不良反应。本研究显示,在甲状腺癌功能性颈淋巴结清扫手术术后给予帕瑞昔布钠镇痛,术后6,12,24 h的VAS评分显著低于CON组(P0.05),可能与患者24 h后疼痛自行缓解有关。甲状腺癌功能性颈淋巴结清扫术,由于手术范围广、创伤大、并发症多,不仅对患者产生躯体上的创伤,更会引起心理创伤,在甲状腺癌治疗过程中患者可能出现各种心理反应,如烦躁、焦虑、恐惧、情绪低落、悲观失望,甚至抑郁厌世。帕瑞昔布钠不仅可改善患者术后疼痛,同时可显著改善患者心理应激状态。有研究8表明帕瑞昔布钠可抑制术后机体应激反应,缓解乳腺癌,根治患者术后免疫功能影响和炎症反应。本研究中,两组患者术前焦虑、抑郁和恐惧评分高,表明患者心理处于应激状态,术后给予帕瑞昔布钠镇痛后,两组患者焦虑、抑郁和恐惧评分均降低,且帕瑞昔布钠组(PAR组)患者焦虑、抑郁和恐惧评分均显著低于CON组(P0.05),表明术后给予帕瑞昔布钠镇痛可改善患者的心理应激状态。本文研究证实帕瑞昔布钠对甲状腺癌手术患者术后镇痛安全有效,可以提高患者术后恢复质量,是一种效果确切、安全的镇痛药物,可用于甲状腺癌功能性颈淋巴结清扫术患者的术后镇痛。REFERENCES 1 PERSEC J,PERSEC Z,BUKOVIC D,et al.Effects of clonidine preemptive analgesia on acute postoperative pain in abdominal surgery J.Coll Antropol,2007,31(4):1071-1075.2 SHEN J C,YANG J J.Research progress of preemptive analgesia J.Pharm Clin Res(药学与临床研究),2010,18(3):208-210.3 SUN E,DEXTER F,MACARIO A.Can an acute pain service be cost-effective J.Anesth Analg,2010,111(4):841-844.4 WITT J K,LINKENAUGER S A,BAKDASH J Z,et al.The long road of pain:chronic pain increases perceived distance J.Exp Brain Rea,2009,192(1):145-148.5 MATTIA C,COLUZZI F,SARZI P P,et 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