盐酸右美托咪啶在OPCABG病人术后认知功能的临床观察
|
摘要
背景：术后认知功能障碍（postoperative cognitive Dysfunction，POCD）是指手术后出现的中枢神经系统并发症，一般表现为认知能力减退、焦虑、记忆减退、语言理解能力和社会融合能力减退等负面效应。有关非体外循环下冠状动脉旁路移植术(Off-pump coronary artery bypass grafting，OPCABG) POCD的研究，病理生理学解释主要集中在神经中枢的损伤，以及微血栓，低灌注和系统性炎症反应等。术中合理用药可以有效降低POCD的发生率，尽量减少因麻醉用药对患者所造成的社会活动、工作及生活自理能力等方面的降低或丧失。
盐酸右美托咪啶(dexmedetomidine，Dex)是一种新型的α2-肾上腺素受体激动剂美托咪定的右旋异构体，具有半衰期短，用量小，中枢α2-肾上腺素受体激动的选择性强(α2: α1=1620:1)的特点。它在麻醉镇静和镇痛方面的辅助作用已经得到广泛的肯定，同时它对血流动力学影响比较小也是优点之一。本研究将右美托咪啶用于非体外循环下冠状动脉旁路移植术患者手术当中，与生理盐水对照组对比其对患者术后认知功能方面的影响，为临床用药提供依据。
目的：本研究旨在观察右美托咪啶对非体外循环下冠状动脉旁路移植术病人术后认识功能的影响，为临床实践提供指导依据。
方法：选择择期手术的非体外循环下冠状动脉旁路移植术患者64例，性别不限，年龄45—65岁，ASAII～III级，心功能I～II级。随机分为对照组(C组)和盐酸右美托咪啶组(D组)，每组32例。D组患者麻醉诱导前持续静脉输注盐酸右美托咪啶，速度为50ng/kg/min，输注时间为30min；麻醉诱导开始后，持续静脉输注盐酸右美托咪啶，速度为7ng/kg/min，直至手术结束，C组患者持续静脉输注等容量0.9%生理盐水。分别在术前、术后第7日对所有患者进行神经心理学测试，观察非体外循环下冠状动脉旁路移植术患者认知功能恢复情况。
结果：两组患者术前神经心理学测试的比较差异无统计学意义（P>0.05）；和术前相比，C组术后第7天数字符号评分升高，数字广度—逆向、小故事—甲评分降低，差异具有统计学意义（P <0.05）；D组术后第7天数字广度—逆向评分降低，差异具有统计学意义（P <0.05）。
和C组相比，D组患者T1、T2、T3时刻HR、SBP、DBP无明显变化（P＞0.05），T4时刻HR、SBP、DBP降低，差异具有统计学意义（P<0.05）；和T1时刻相比，C组患者T4时刻HR、SBP、DBP升高，差异具有统计学意义（P<0.05）。
和C组相比，D组患者术中静脉输注丙泊酚和舒芬太尼总量降低，差异具有统计学意义（P<0.05）。
C，D两组患者术后麻醉苏醒后，均有不同程度的认知功能障碍发生， C组患者有6例发生了术后认知功能障碍，发生率为18.8%；D组患者有2例发生了术后认知功能障碍，发生率为6.3%；和C组相比，D组术后认知功能障碍发生率降低，差异具有统计学意义（P <0.05），术后躁动，谵妄等发生率均较低；D组疼痛，躁动，认知功能不全发生率较低于C组。
结论：盐酸右美托咪啶对于非体外循环下冠状动脉旁路移植术病人安全有效，能够维持稳定的血流动力学，其疼痛、躁动、认知功能不全发生率明显降低；能够有效抑制气管插管引起的应激反应，提供稳定的血流动力学；能够有效辅助镇痛并减少患者阿片类镇痛药和丙泊酚的用量，值得临床推广。
Background: Postoperative cognitive dysfunction (POCD) is the central nervoussystem complications after surgery, the general performance are cognitive declining, anxiety,impaired memory, the negative effect which the ability of language comprehension andsocial integration have diminished. For off-pump coronary artery bypass grafting,the studiesof POCD, and pathophysiology explained mainly concentrated in the nerve center of thedamage, and microthrombi, hypoperfusion, and systemic inflammatory response. Rationaldrug use in surgery can effectively reduce the incidence of POCD of minimizing the socialactivities caused by narcotic medication for patients, the reduction or loss of work andliving skills and other aspects.
America care, the right of hydrochloric acid microphone set (patients todexmedetomidine, Dex) is a novel α2-adrenergic receptor agonist, beauty care given theright-handed isomers in microphone, has a short half-life, dosage, the hub of α2-adrenergicreceptor agonist selectivity (of α2: α1=1620:1) features. Supporting role in sedation andanalgesia has been widely recognized, while its hemodynamic effects are relatively small, isone of the advantages. To the right dexmedetomidine in this study for patients withnon-pump coronary artery bypass grafting surgery, its impact on postoperative cognitivefunction in patients with compared with the saline control group, to provide a basis forclinical treatment.
Objective: This study aimed to investigate the influence of dexmedetomidine givencognitive function after coronary artery bypass grafting patients without cardiopulmonarybypass, provide a basis for guiding clinical practice.
Methods:64cases of elective surgery patients with coronary artery bypass graftingwithout cardiopulmonary bypass, gender
Not limited to, age45-65years old, ASAII III class, cardiac function I Level II. Wererandomly divided into control group (group C) and hydrochloric acid right dexmedetomidinegroup (D),32cases in each group. Group D patients before induction of anesthesiacontinuous intravenous infusion of hydrochloric acid right the prop microphone set speed50ng/kg/min, infusion time of30min; induction of anesthesia, after the start of continuousintravenous infusion of hydrochloric acid dexmedetomidine given speed7ng/kg/min, until the end of surgery, group C patients with sustained intravenous infusion and an equalvolume of0.9%saline. Respectively, in the preoperative and postoperative7days for allpatients with neuropsychological tests, observation of off-pump coronary artery bypassgrafting in patients with cognitive function in the recovery of
Results: The neuropsychological tests in two groups of patients before was nosignificant difference (P>0.05);
Compared to the preoperative increase in group C after7days Digit Symbol score, digitspan-Reverse little story-A score lower, the difference was statistically significant (P<0.05); D group after7days, digital breadth-Reverse score lower, the difference wasstatistically significant (P <0.05).
Compared to group C, group D patients with T1, T2, T3time the HR, SBP and DBP nosignificant change (P>005), T4moment the HR SBP and DBP decreased, the differencewas statistically significant (P <0.05); and T1time, group C patients with T4moment HRSBP and DBP increased, the difference was statistically significant (P <0.05).
Compared to Group C Group D patients undergoing intravenous infusion of propofoland sufentanil total lower, the difference was statistically significant (P <0.05).
C and D, two groups of patients after recovery from anesthesia, the varying degrees ofcognitive dysfunction, six cases of postoperative cognitive dysfunction group C patients, theincidence rate of18.8%; Group D patients had two cases postoperative cognitive dysfunction,the incidence rate of6.3%; and group C, D, postoperative cognitive dysfunction reduced theincidence of a statistically significant difference (P <0.05), postoperative agitation, delirium,etc. The low incidence; Group D pain, restlessness, low incidence of cognitive dysfunctionin the C group.
Conclusion: dexmedetomidine hydrochloride given for the safety of off-pump coronaryartery bypass graft surgery patients, able to maintain stable hemodynamics, its pain, agitation,cognitive dysfunction was significantly reduced; can effectively inhibit the endotracheal tubecaused by the stress response and hemodynamic stability; able to effectively assist theanalgesic effect and reduce the amount of patients with opioid analgesics and propofol, andworthy of promotion.
盐酸右美托咪啶(dexmedetomidine，Dex)是一种新型的α2-肾上腺素受体激动剂美托咪定的右旋异构体，具有半衰期短，用量小，中枢α2-肾上腺素受体激动的选择性强(α2: α1=1620:1)的特点。它在麻醉镇静和镇痛方面的辅助作用已经得到广泛的肯定，同时它对血流动力学影响比较小也是优点之一。本研究将右美托咪啶用于非体外循环下冠状动脉旁路移植术患者手术当中，与生理盐水对照组对比其对患者术后认知功能方面的影响，为临床用药提供依据。
目的：本研究旨在观察右美托咪啶对非体外循环下冠状动脉旁路移植术病人术后认识功能的影响，为临床实践提供指导依据。
方法：选择择期手术的非体外循环下冠状动脉旁路移植术患者64例，性别不限，年龄45—65岁，ASAII～III级，心功能I～II级。随机分为对照组(C组)和盐酸右美托咪啶组(D组)，每组32例。D组患者麻醉诱导前持续静脉输注盐酸右美托咪啶，速度为50ng/kg/min，输注时间为30min；麻醉诱导开始后，持续静脉输注盐酸右美托咪啶，速度为7ng/kg/min，直至手术结束，C组患者持续静脉输注等容量0.9%生理盐水。分别在术前、术后第7日对所有患者进行神经心理学测试，观察非体外循环下冠状动脉旁路移植术患者认知功能恢复情况。
结果：两组患者术前神经心理学测试的比较差异无统计学意义（P>0.05）；和术前相比，C组术后第7天数字符号评分升高，数字广度—逆向、小故事—甲评分降低，差异具有统计学意义（P <0.05）；D组术后第7天数字广度—逆向评分降低，差异具有统计学意义（P <0.05）。
和C组相比，D组患者T1、T2、T3时刻HR、SBP、DBP无明显变化（P＞0.05），T4时刻HR、SBP、DBP降低，差异具有统计学意义（P<0.05）；和T1时刻相比，C组患者T4时刻HR、SBP、DBP升高，差异具有统计学意义（P<0.05）。
和C组相比，D组患者术中静脉输注丙泊酚和舒芬太尼总量降低，差异具有统计学意义（P<0.05）。
C，D两组患者术后麻醉苏醒后，均有不同程度的认知功能障碍发生， C组患者有6例发生了术后认知功能障碍，发生率为18.8%；D组患者有2例发生了术后认知功能障碍，发生率为6.3%；和C组相比，D组术后认知功能障碍发生率降低，差异具有统计学意义（P <0.05），术后躁动，谵妄等发生率均较低；D组疼痛，躁动，认知功能不全发生率较低于C组。
结论：盐酸右美托咪啶对于非体外循环下冠状动脉旁路移植术病人安全有效，能够维持稳定的血流动力学，其疼痛、躁动、认知功能不全发生率明显降低；能够有效抑制气管插管引起的应激反应，提供稳定的血流动力学；能够有效辅助镇痛并减少患者阿片类镇痛药和丙泊酚的用量，值得临床推广。
Background: Postoperative cognitive dysfunction (POCD) is the central nervoussystem complications after surgery, the general performance are cognitive declining, anxiety,impaired memory, the negative effect which the ability of language comprehension andsocial integration have diminished. For off-pump coronary artery bypass grafting,the studiesof POCD, and pathophysiology explained mainly concentrated in the nerve center of thedamage, and microthrombi, hypoperfusion, and systemic inflammatory response. Rationaldrug use in surgery can effectively reduce the incidence of POCD of minimizing the socialactivities caused by narcotic medication for patients, the reduction or loss of work andliving skills and other aspects.
America care, the right of hydrochloric acid microphone set (patients todexmedetomidine, Dex) is a novel α2-adrenergic receptor agonist, beauty care given theright-handed isomers in microphone, has a short half-life, dosage, the hub of α2-adrenergicreceptor agonist selectivity (of α2: α1=1620:1) features. Supporting role in sedation andanalgesia has been widely recognized, while its hemodynamic effects are relatively small, isone of the advantages. To the right dexmedetomidine in this study for patients withnon-pump coronary artery bypass grafting surgery, its impact on postoperative cognitivefunction in patients with compared with the saline control group, to provide a basis forclinical treatment.
Objective: This study aimed to investigate the influence of dexmedetomidine givencognitive function after coronary artery bypass grafting patients without cardiopulmonarybypass, provide a basis for guiding clinical practice.
Methods:64cases of elective surgery patients with coronary artery bypass graftingwithout cardiopulmonary bypass, gender
Not limited to, age45-65years old, ASAII III class, cardiac function I Level II. Wererandomly divided into control group (group C) and hydrochloric acid right dexmedetomidinegroup (D),32cases in each group. Group D patients before induction of anesthesiacontinuous intravenous infusion of hydrochloric acid right the prop microphone set speed50ng/kg/min, infusion time of30min; induction of anesthesia, after the start of continuousintravenous infusion of hydrochloric acid dexmedetomidine given speed7ng/kg/min, until the end of surgery, group C patients with sustained intravenous infusion and an equalvolume of0.9%saline. Respectively, in the preoperative and postoperative7days for allpatients with neuropsychological tests, observation of off-pump coronary artery bypassgrafting in patients with cognitive function in the recovery of
Results: The neuropsychological tests in two groups of patients before was nosignificant difference (P>0.05);
Compared to the preoperative increase in group C after7days Digit Symbol score, digitspan-Reverse little story-A score lower, the difference was statistically significant (P<0.05); D group after7days, digital breadth-Reverse score lower, the difference wasstatistically significant (P <0.05).
Compared to group C, group D patients with T1, T2, T3time the HR, SBP and DBP nosignificant change (P>005), T4moment the HR SBP and DBP decreased, the differencewas statistically significant (P <0.05); and T1time, group C patients with T4moment HRSBP and DBP increased, the difference was statistically significant (P <0.05).
Compared to Group C Group D patients undergoing intravenous infusion of propofoland sufentanil total lower, the difference was statistically significant (P <0.05).
C and D, two groups of patients after recovery from anesthesia, the varying degrees ofcognitive dysfunction, six cases of postoperative cognitive dysfunction group C patients, theincidence rate of18.8%; Group D patients had two cases postoperative cognitive dysfunction,the incidence rate of6.3%; and group C, D, postoperative cognitive dysfunction reduced theincidence of a statistically significant difference (P <0.05), postoperative agitation, delirium,etc. The low incidence; Group D pain, restlessness, low incidence of cognitive dysfunctionin the C group.
Conclusion: dexmedetomidine hydrochloride given for the safety of off-pump coronaryartery bypass graft surgery patients, able to maintain stable hemodynamics, its pain, agitation,cognitive dysfunction was significantly reduced; can effectively inhibit the endotracheal tubecaused by the stress response and hemodynamic stability; able to effectively assist theanalgesic effect and reduce the amount of patients with opioid analgesics and propofol, andworthy of promotion.
引文
[1] Moller J T, Cluimans P, Rasmussen L S, et al.Long-term postoperative cognitivedysfunction in the elderly: ISPOCD1study. Lancet,1998,351(9117):857—861.
[2] Canet J,Raeder J, Rasmussen L S, et al. Cognitive dysfunction after minor surgery inthe elderly[J].ActaAnaesthesiolScand,2003,47(10):1204-1210.
[3] Criswell H E, Ming Z, Pleasant N, et al. Macrokinetic analysis of blockade ofNMDA2gated Currents by substituted alcohols, alkanes and ethers[J]. Brain Res,2004,1015(1-2):107-113.
[4] Naruo H, Onizuka S, Prince D, et al. Sevoflurane blocks cholin-ergic synaptictransmission postsynap tically but does not affect short-term potentiation [J].Anesthesiology,2005,102(5):920-928.
[5] Bruce DI，et a l. Anesth，Analg，1983;62:84
[6] Crosby C, Culley DJ, Baxter M G, et al. Spatial memory performance2weeks aftergeneral anesthesia in adult rats [J]. Anesth Analg,2005,102(5):1389-1392.
[7]贾宝森，张宏。异氟醚及七氟醚复合麻醉下老年患者脑氧饱和度与术后认知功能的关系[J]。中华麻醉学杂志,2004,24(5):348-351。
[8] Jones MJT et al. Br Med J1990;300:1683.
[9]王贤裕，田玉科，安珂，等．氯胺酮对术后大鼠海马NMDAR亚单位蛋白表达的影响[J]．华中科技大学学报(医学版)，2005，34(3):372-3741．
[10]Campbell DNC et al. Anesthesia.1993;48:422.
[11]Williams RP，et al.J Am Med Associ,1995;274:44.
[12]Williams-Russo P, Sharrock N E, Mattis S, etal.Cognitive effects after epidural vsgeneral anesthesia in older adults. A random izedtrial[J]. JAMA,1995,274:44-50.
[13]Gregory L.Bryson FRCPC MSc,Anna Wyand MD.Evidence-based clinicalupdate:General anesthesia and the risk of delirium and postoperative cognitiveDysfunction [J].CAN J ANESTH2006,53(7):669–677
[14]Bourin M, Ripoll N, Dailly E. Nicotinic receptors and Alzheimer sdisease[J].CurrMedResOpin,2003,19:169-177.
[15]GanguliM,DodgeHH, Shen C, eta.l Alzheimerdisease andmortali-ty: a15-yearepidemiological study[J].Arch Neuro,l2005,62:779-784.
[16]Ueno T, Iguro Y, YamamotoH.Serial measurement of seru S-100β protein as a marker ofcerebra damage after cardiac Surgery Ann ThoracSurg.2003,75:1892-1897.
[17]Weiskopf RB, Kramer JH, Viele M, et a.l Acute severe isovolemicanemia impairscognitive function andmemory in humans[J].Anes-thesiology,2000,92:1646-1652.
[18]Canet J,Raeder J, Rasmussen L S, et al. Cognitive dysfunction after minor surgery inthe elderly[J].ActaAnaesthesiolScand,2003,47(10):1204-1210.
[19]朱长庚．神经解剖学[M]．北京:人民卫生出版社，2002：202-204．
[20]Gregory L.Bryson FRCPC MSc,Anna Wyand MD.Evidence-based clinicalupdate:General anesthesia and the risk of delirium and postoperative cognitiveDysfunction [J].CAN J ANESTH2006,53(7):669–677
[21]孙静,阚耀东。S100β蛋白的生物学特性及其在临床中的应用进展[J].诊断学理论与实践,2005,4(2):172-174.
[22]Zimmer DB,Cornwall EH,landar A,Song W,the S-100protein family:function, andexpression.Brain Res Bull1995;37:417-429.
[23]Donato R Perspectives in S-100protein biology.Review article [J]. Cell Calcium,1991,12(10):713-726.
[24]陈俊,何国厚,江荣翠。急性脑梗塞患者S-100蛋白的动态检测及其与临床的相关性研究[J].中国免疫学杂志,2004,20(12):869-872.
[25]Schafer BW,H eizm ann CW. The S100family of EF-hand calcium-Binding proteins:functions and pathology[J]. Trends Biochem Sc I1996,21(4):134-140.
[26]李守霞,邓群颖,赵瑞月。 S-100β蛋白检测对神经系统损伤早期诊断临床应用进展[J].中国误诊学杂志,2002,2(8):1156-1158。
[27]Mussack T,Hauser C,Klauss V,TatσF,Rieger J,Ruppert V,Jochum M,Hoffmann U.SerumS-100β protein levels during and after successful carotid artery stenting or carotidendarterectomy.J Endovasc Ther2006;13:39-46
[28]Nygaard O,Langbakk B,RomnerB Age–and sex-related changes of s-100proteincon-centrations in cerebrospinal fluid and serum in patients with no previous history ofneurological disorder.Clin Chem1997;43:541-543.
[29]Ali MS Harmer M,Vaughan R.Serum s100protein as a marker of cerebral damageduring cardiac surgery.Br J Anaesth2000;85:287-298。
[30]Zimmer DB,Cornwall EH,landar A,Song W,the S-100protein family:function, andexpression.Brain Res Bull1995;37:417-429.
[31]Donato R. Perspectives in S-100protein biology.Review article [J]. Cell Calcium,1991,12(10):713-726.
[32]Ohyu J, Endo A, Itoh M, et a.l Hypocapnia under hypotension in-duces apoptoticneuronal cell death in the hippocampus of newbornrabbits[J]. PediatrRes,2000,48:24-29.
[33]Kapural M K rizanac-Bengez L j,Barnett G, Perl J, Masaryk T,Apollo D, RasmussenP,Mayberg. M R, Janigro D.Serum S-100beta as a possible marker of blood-brainbarrier disruption.Brain Res2002;940:102-104
[34]Ramsey MA, Luterman DL. Dexmedetonidine as a total intravenous anesthestic agent[J].Anesthesiology,2004;101:778-781.
[35]兰州军区总医院麻醉科刘东综述上海长海医院麻醉科于布为申校右旋美托咪啶用的药理和临床应用（国外医学）麻醉学与复苏分册1995年第18卷第4期
[36]CalzadaBC,DeArtinanoAA.,Alpha2-adrenorecetorsubtypes[J].Pharmacolkes,2001,44;195-208.
[37]Khan ZP,Ferguson CN,Jones RM,Alpha-2and imidazoline receptor agonists:theirpharmacology and therapeutic mole[J].Anesthesia,1999,54:146-165.
[38]Scheinin H, Aantaa R, Anttila M,. Reversal of the sedative and sympatholytic effects ofdexmedetomidine with a specific alpha2-adrenoceptor antagonist atipamezole:apharmacodynamic and kinetic study in healthy volunteers. Anesthesiology1998;89(3):574-584.
[39]Penttila J，Helminen A，Anttila M，et al.Cardiovascular and parasympathetic effects ofdexmetomidine in healthy subjects[J].Canadian J physiology and pharmacology，2004;82:359-362.
[40]Bekker AY,Basile J,Gold M,et al. Dexmedetomidine for awake carotid endarterectomy:efficacy, hemodynamic profile, and side effects..J Neurosurg Anesthesiol2004;16(2):126–135.
[41]Tobias JD.Dexmedetomidine:appications in pediatric critical.care and pediatric.anesthesiology. pedatric critical care medicine.2007,8(2):115-131.
[42]Belleville,ward DS,Bloor BC,etal.Effects of intravenous dexmedetomidine in humans.Anesthesiology1992,77:1125-1133
[43]Hall JE,Uhrich TD,Barney JA,et al.Sedative,annestic and analgesic properties of smalldose dexmedetomidine infusions Anesth&Analg,200090(3):699-705.
[44]R.M.Venn.Effects of dexmedetomidine on adrenocortical function,and the cardi-ovascular，endocrine and inflammatory responses in postoperative patients needingsedation in the intensive unit[J].BJA，2001，86：650-656.
[45]冯征；王志萍；段世明；曾因明；α2肾上腺素受体激动药及其临床应用进展.《国外医学》麻醉学与复苏分册,1997,18(5):273-276.
[46]Riker，Richard，Shehabi，et al.Dexmedetomidine vs Midazolam for Se-dation ofCritically Ill Patients：A Randomized Trial[J].JAMA，2009，301(5)：489-499.
[47]Venn RM, Bradshaw CJ, Spencer R, et al. Preliminary UK experience ofdexmedetomidine, a novel agent for postoperative sedation in the intensive careunit.Anaesthesia1999;54(12):1136–1142.
[48]Ruokonen E,Parviainen I,Jakob S M， et al.Dexmedetomidine versus propo-folmidazolam for long-term sedation during mechanical ventilation[J]. Intensive CareMed，2009，35(2)：282-290.
[49]Martin.The role of the alpha2adrenoceptor agonist dexmedetomidine in postsurgicalsedation in the intensive care unit[J].Int Care Med，2003，18：29-41.
[50]Moore TA,Markert JM,Knowlton RC.Dexmedetonidine sedation during awakecraniotomy for seizare resection:effects on electrocorgraphy[J].J Neurosurg Anesthesiol,2007,19:38-44.
[51]曲歌，刘铁成.右美托嘧啶辅助冠状动脉旁路移植手术全身麻醉的作用[J].中国实验诊断学，2011（15）
[52]Elbaradie S, EIMahalawy FH, Solyman AH. Dexmedetomidine vs.propofol forshort2term sedation of postoperativemechanically venti2lated patients[J]. J Egyp t NatlCanc Inst,2004,16(3):1532158.
[53]Corbett SM, Rebuck JA, Greene CM, et al. Dexmedetomidine does not imp rove patientsatisfaction when compared to p ropofol during mechanical ventilation[J]. CritCareMed,2005,33(5):9402945.
[54]Moore TA, Markert JM, Knowlton RC. Dexmedetonidine sedation during awakecraniotomy for seizare resection: effects on electrocorgraphy[J]. J NeurosurgAnesthesiol,2007,19:38-44./2.
[55]Ard J,Bekker A,Doyle W.Dexmedetonidine in awake craniotomy:Atechnical note[J].Surg Neurol,2005,63:114-117.
[56]Venn RM, Grounds RM. Comparison between dexmedetomidineand p ropofol forsedation in the intensive care unit patient and cli2nician percep tions[J]. Br J Anaesth,2001,87(5):6842690.
[57]Bradley C.Dexmedetomidine-a novel sedative for postoperative sedation[J]. IntensiveCrit Care Nurs，2000，16：328-329.
[58]Ard J,Doyle W,Bebber A.Awake craniotomy with dexmedetonidine in pediatricpatients[J].J Neurosurg Anesthesiol,2003,15:263-266.
[59]vikkila M，etal,Anemtheaiology,1993;48;402.
[60]Jackola Metal,Br J. Aneaet,1992;68;570.
[61]Bloom M,Beric A,Bekker A.Dexmedetonidine infusion and somatosensory evokedpotentials[J].J Neurosurg Anesthesiol.2001,13;320-322.
[62]Mason KP,ZglesZew ski SE,Dearden JL,et al.Dexmedetonidine for pediatric sedation forcomputed tomography imaging studies[J].Anesth Analg,2006,103:57-62.
[63]Berkenbosch JW,Wankum PC,Tobias JD.Prospective evaluation of dexmedetonidine fornoninvasive procedural sedation in children[J].Pediatric Crit Care Med,2005,6:435-439.
[64]Talke P, Chen R, Thomas B,et al. The hemodynamic and adrenergic effects ofperioperative dexmedetomidine infusion after vascular surgery. Anesth&Analg2000;90(4):834-839
[65]Yildiz M,Tavlan A,Tunur S,et al.Effect of dexmedetonidine on haemodynamic responsesto laryngoscopy and intubation:perioperative haemodynamics and anaesthetic require-ments[J].Drugs RD,2006,7:43-52.
[66]Maldonado JR，Wysong A，Vander Starre PJA，et al.Dexmedetomidine and the reductionof postoperative delirium after cardiac surgery[J].American Psychiatric Association，2008.
[67]Scheinin B,Lindgren L,Randell T,et al.Dexmedetonidine attenuates sympathoadrenalresponses to tracheal intubation and reduces the need for thiopentone and peroperativefentanyl[J].Br J Anaesth,1992,68:126-131.
[68]Fragen RJ,Fitzgerald PC.Effect of dexmedetonidine on the minimum alveolarconcentration(MAC)of sevoflurane in adults age55to70years[J].J Cline Anesth.1999,11:466-470.
[69]Jaionen J，Hynynen M，Kuitunen A，et al. Dexmedetomidine as an anesthetic adjunct incoronary artery bypass grafting. Anesthesiology,1997;86(2):331-345.
[70]Aho Metal,Aneath Analy,1992;75;940.
[71]Horvaeh R etal,Aneath Analy,1992;74;56.
[72]Scheinim Hetal, Aneatheaiology,1993;78;65.
[1] Monk TG， weldon BC，Garvan CW，et al. predietors of eognitive dysfunction aftermajor non-eardiaesurgery〔J」.Anesthesiology，2008，108(1):18-30.
[2] Steinmetz J， Christensen KB， Rasmussen LS，et al.Long-terme consequenees ofPostoperative eognitive dysfunction{J].Anesthesiolog丛2009.110(3):548-55.。
[3] Dodds C,Allison J.Postoperative cognitive deficit in the elderly surgical patient.Rr JAnaesth,1998;81(3):449.
[4] Newman S P. Analysis and interpretation of neuropsychologic tests in cardiacsurgery[J].Ann Thorac Surg.1995,59(5):1351-1355.
[5] Moler JT，Cluitmans P，Rasmussen LS，et al.Long-term postoperative cognitivedysfunetion in the elderly:ISPOCD1stUdy[J].The Laneet，1998，351:857-861.
[6] Bekker AY,Weeks EJ.Cognitive funetion afteranaesthesia in the elderly[J]Best PraetReClin Anaesthesiol，2003，17:259-72.
[7] Pratico C， Quattrone D， LueantoT,et al.Drugs of anesthesia acting on centralcholinergic system may eause post-operation eognitive dysfunction anddelirium[J].MedHyPothese，2005，65(5):972-982
[8] Parik SS，Chung F.Postoperative delirium in the elderly[J].Anesth Analg，1995，80:1223-32.
[9]王春燕，吴新民。全身麻醉术后对中老年病人认知功能的影目可[J]。中华麻醉学杂志，2002，22(6):332-335.
[10]蔡一榕，薛张刚，朱彪。患者术后认知功能障碍的危险因素分析[J]。临床麻醉学杂志，2006，22(8):608-610.
[11]易善永等,心理行为干预对心脏瓣膜置换术后早期认知功能障碍的影响[J]。中国行为医学科学，2005，6。
[12] Wang Y，Sands LP，VaurioL，et al.The effects of Postoperative Pain and itsmanagement on Postoperative cognitive dysfunctlon[J].Am J Geriati Psyehiatry.2007，15(l):50-59
[13] Cohendy，Robert，Brougere， et al.Anaesthesia in the older Patient[J].Current OPinionin ClinicalNutrit Metabolic Care，2005，8（1）：17-21
[14]李丽萍，江晓，葛衡江。术后疼摘对老年患者术后早期认知功能的影响[J]。重庆医学，2009，38（14）：212-215
[15]张洋等，盐酸右美托咪定的药理作用及其在全身麻醉中的应用。医学临床研究，2011，28（3）
[16] Kanda H，Kurosawa T et al.Effeet of dexlnedetomidine on anesthetic requirements ineardiovaseular sulgery[J].Masui.2009.58(12):1496-1500
[17] Kerdawy H，Gouda N，Kamal H.Dexmedetomidine as anaesthetic adjunet for Patientsundergoing off-PumP coronary artery byPass grafting[J].EgyPtian Joumal ofAnaesthesia，2004.20:29-34
[18]王珊珊，盐酸右美托咪定对高血压患者全麻诱导及气管插管期血流动力学及应激反应的影响[J]。江苏大学，2011
[19]蔡淑女，方军。异丙酚和七氟醚对老年乳腺癌患者术中应激反应和术后认知功能的影响[J]，全科医学临床与教育，2011，02（9）。
[20]朱志华，李龙云，张闻宇。右旋美托咪啶对预防开胸手术患者麻醉苏醒期躁动的临床观察。中国实验诊断学，2011,5。
[21]杨建英，申屠燕琴，裘卫东，吴跃。心率变异性评价盐酸右美托咪定在无痛人流术中的抗焦虑作用[J]。解放军药学，2010,4。
[2] Canet J,Raeder J, Rasmussen L S, et al. Cognitive dysfunction after minor surgery inthe elderly[J].ActaAnaesthesiolScand,2003,47(10):1204-1210.
[3] Criswell H E, Ming Z, Pleasant N, et al. Macrokinetic analysis of blockade ofNMDA2gated Currents by substituted alcohols, alkanes and ethers[J]. Brain Res,2004,1015(1-2):107-113.
[4] Naruo H, Onizuka S, Prince D, et al. Sevoflurane blocks cholin-ergic synaptictransmission postsynap tically but does not affect short-term potentiation [J].Anesthesiology,2005,102(5):920-928.
[5] Bruce DI，et a l. Anesth，Analg，1983;62:84
[6] Crosby C, Culley DJ, Baxter M G, et al. Spatial memory performance2weeks aftergeneral anesthesia in adult rats [J]. Anesth Analg,2005,102(5):1389-1392.
[7]贾宝森，张宏。异氟醚及七氟醚复合麻醉下老年患者脑氧饱和度与术后认知功能的关系[J]。中华麻醉学杂志,2004,24(5):348-351。
[8] Jones MJT et al. Br Med J1990;300:1683.
[9]王贤裕，田玉科，安珂，等．氯胺酮对术后大鼠海马NMDAR亚单位蛋白表达的影响[J]．华中科技大学学报(医学版)，2005，34(3):372-3741．
[10]Campbell DNC et al. Anesthesia.1993;48:422.
[11]Williams RP，et al.J Am Med Associ,1995;274:44.
[12]Williams-Russo P, Sharrock N E, Mattis S, etal.Cognitive effects after epidural vsgeneral anesthesia in older adults. A random izedtrial[J]. JAMA,1995,274:44-50.
[13]Gregory L.Bryson FRCPC MSc,Anna Wyand MD.Evidence-based clinicalupdate:General anesthesia and the risk of delirium and postoperative cognitiveDysfunction [J].CAN J ANESTH2006,53(7):669–677
[14]Bourin M, Ripoll N, Dailly E. Nicotinic receptors and Alzheimer sdisease[J].CurrMedResOpin,2003,19:169-177.
[15]GanguliM,DodgeHH, Shen C, eta.l Alzheimerdisease andmortali-ty: a15-yearepidemiological study[J].Arch Neuro,l2005,62:779-784.
[16]Ueno T, Iguro Y, YamamotoH.Serial measurement of seru S-100β protein as a marker ofcerebra damage after cardiac Surgery Ann ThoracSurg.2003,75:1892-1897.
[17]Weiskopf RB, Kramer JH, Viele M, et a.l Acute severe isovolemicanemia impairscognitive function andmemory in humans[J].Anes-thesiology,2000,92:1646-1652.
[18]Canet J,Raeder J, Rasmussen L S, et al. Cognitive dysfunction after minor surgery inthe elderly[J].ActaAnaesthesiolScand,2003,47(10):1204-1210.
[19]朱长庚．神经解剖学[M]．北京:人民卫生出版社，2002：202-204．
[20]Gregory L.Bryson FRCPC MSc,Anna Wyand MD.Evidence-based clinicalupdate:General anesthesia and the risk of delirium and postoperative cognitiveDysfunction [J].CAN J ANESTH2006,53(7):669–677
[21]孙静,阚耀东。S100β蛋白的生物学特性及其在临床中的应用进展[J].诊断学理论与实践,2005,4(2):172-174.
[22]Zimmer DB,Cornwall EH,landar A,Song W,the S-100protein family:function, andexpression.Brain Res Bull1995;37:417-429.
[23]Donato R Perspectives in S-100protein biology.Review article [J]. Cell Calcium,1991,12(10):713-726.
[24]陈俊,何国厚,江荣翠。急性脑梗塞患者S-100蛋白的动态检测及其与临床的相关性研究[J].中国免疫学杂志,2004,20(12):869-872.
[25]Schafer BW,H eizm ann CW. The S100family of EF-hand calcium-Binding proteins:functions and pathology[J]. Trends Biochem Sc I1996,21(4):134-140.
[26]李守霞,邓群颖,赵瑞月。 S-100β蛋白检测对神经系统损伤早期诊断临床应用进展[J].中国误诊学杂志,2002,2(8):1156-1158。
[27]Mussack T,Hauser C,Klauss V,TatσF,Rieger J,Ruppert V,Jochum M,Hoffmann U.SerumS-100β protein levels during and after successful carotid artery stenting or carotidendarterectomy.J Endovasc Ther2006;13:39-46
[28]Nygaard O,Langbakk B,RomnerB Age–and sex-related changes of s-100proteincon-centrations in cerebrospinal fluid and serum in patients with no previous history ofneurological disorder.Clin Chem1997;43:541-543.
[29]Ali MS Harmer M,Vaughan R.Serum s100protein as a marker of cerebral damageduring cardiac surgery.Br J Anaesth2000;85:287-298。
[30]Zimmer DB,Cornwall EH,landar A,Song W,the S-100protein family:function, andexpression.Brain Res Bull1995;37:417-429.
[31]Donato R. Perspectives in S-100protein biology.Review article [J]. Cell Calcium,1991,12(10):713-726.
[32]Ohyu J, Endo A, Itoh M, et a.l Hypocapnia under hypotension in-duces apoptoticneuronal cell death in the hippocampus of newbornrabbits[J]. PediatrRes,2000,48:24-29.
[33]Kapural M K rizanac-Bengez L j,Barnett G, Perl J, Masaryk T,Apollo D, RasmussenP,Mayberg. M R, Janigro D.Serum S-100beta as a possible marker of blood-brainbarrier disruption.Brain Res2002;940:102-104
[34]Ramsey MA, Luterman DL. Dexmedetonidine as a total intravenous anesthestic agent[J].Anesthesiology,2004;101:778-781.
[35]兰州军区总医院麻醉科刘东综述上海长海医院麻醉科于布为申校右旋美托咪啶用的药理和临床应用（国外医学）麻醉学与复苏分册1995年第18卷第4期
[36]CalzadaBC,DeArtinanoAA.,Alpha2-adrenorecetorsubtypes[J].Pharmacolkes,2001,44;195-208.
[37]Khan ZP,Ferguson CN,Jones RM,Alpha-2and imidazoline receptor agonists:theirpharmacology and therapeutic mole[J].Anesthesia,1999,54:146-165.
[38]Scheinin H, Aantaa R, Anttila M,. Reversal of the sedative and sympatholytic effects ofdexmedetomidine with a specific alpha2-adrenoceptor antagonist atipamezole:apharmacodynamic and kinetic study in healthy volunteers. Anesthesiology1998;89(3):574-584.
[39]Penttila J，Helminen A，Anttila M，et al.Cardiovascular and parasympathetic effects ofdexmetomidine in healthy subjects[J].Canadian J physiology and pharmacology，2004;82:359-362.
[40]Bekker AY,Basile J,Gold M,et al. Dexmedetomidine for awake carotid endarterectomy:efficacy, hemodynamic profile, and side effects..J Neurosurg Anesthesiol2004;16(2):126–135.
[41]Tobias JD.Dexmedetomidine:appications in pediatric critical.care and pediatric.anesthesiology. pedatric critical care medicine.2007,8(2):115-131.
[42]Belleville,ward DS,Bloor BC,etal.Effects of intravenous dexmedetomidine in humans.Anesthesiology1992,77:1125-1133
[43]Hall JE,Uhrich TD,Barney JA,et al.Sedative,annestic and analgesic properties of smalldose dexmedetomidine infusions Anesth&Analg,200090(3):699-705.
[44]R.M.Venn.Effects of dexmedetomidine on adrenocortical function,and the cardi-ovascular，endocrine and inflammatory responses in postoperative patients needingsedation in the intensive unit[J].BJA，2001，86：650-656.
[45]冯征；王志萍；段世明；曾因明；α2肾上腺素受体激动药及其临床应用进展.《国外医学》麻醉学与复苏分册,1997,18(5):273-276.
[46]Riker，Richard，Shehabi，et al.Dexmedetomidine vs Midazolam for Se-dation ofCritically Ill Patients：A Randomized Trial[J].JAMA，2009，301(5)：489-499.
[47]Venn RM, Bradshaw CJ, Spencer R, et al. Preliminary UK experience ofdexmedetomidine, a novel agent for postoperative sedation in the intensive careunit.Anaesthesia1999;54(12):1136–1142.
[48]Ruokonen E,Parviainen I,Jakob S M， et al.Dexmedetomidine versus propo-folmidazolam for long-term sedation during mechanical ventilation[J]. Intensive CareMed，2009，35(2)：282-290.
[49]Martin.The role of the alpha2adrenoceptor agonist dexmedetomidine in postsurgicalsedation in the intensive care unit[J].Int Care Med，2003，18：29-41.
[50]Moore TA,Markert JM,Knowlton RC.Dexmedetonidine sedation during awakecraniotomy for seizare resection:effects on electrocorgraphy[J].J Neurosurg Anesthesiol,2007,19:38-44.
[51]曲歌，刘铁成.右美托嘧啶辅助冠状动脉旁路移植手术全身麻醉的作用[J].中国实验诊断学，2011（15）
[52]Elbaradie S, EIMahalawy FH, Solyman AH. Dexmedetomidine vs.propofol forshort2term sedation of postoperativemechanically venti2lated patients[J]. J Egyp t NatlCanc Inst,2004,16(3):1532158.
[53]Corbett SM, Rebuck JA, Greene CM, et al. Dexmedetomidine does not imp rove patientsatisfaction when compared to p ropofol during mechanical ventilation[J]. CritCareMed,2005,33(5):9402945.
[54]Moore TA, Markert JM, Knowlton RC. Dexmedetonidine sedation during awakecraniotomy for seizare resection: effects on electrocorgraphy[J]. J NeurosurgAnesthesiol,2007,19:38-44./2.
[55]Ard J,Bekker A,Doyle W.Dexmedetonidine in awake craniotomy:Atechnical note[J].Surg Neurol,2005,63:114-117.
[56]Venn RM, Grounds RM. Comparison between dexmedetomidineand p ropofol forsedation in the intensive care unit patient and cli2nician percep tions[J]. Br J Anaesth,2001,87(5):6842690.
[57]Bradley C.Dexmedetomidine-a novel sedative for postoperative sedation[J]. IntensiveCrit Care Nurs，2000，16：328-329.
[58]Ard J,Doyle W,Bebber A.Awake craniotomy with dexmedetonidine in pediatricpatients[J].J Neurosurg Anesthesiol,2003,15:263-266.
[59]vikkila M，etal,Anemtheaiology,1993;48;402.
[60]Jackola Metal,Br J. Aneaet,1992;68;570.
[61]Bloom M,Beric A,Bekker A.Dexmedetonidine infusion and somatosensory evokedpotentials[J].J Neurosurg Anesthesiol.2001,13;320-322.
[62]Mason KP,ZglesZew ski SE,Dearden JL,et al.Dexmedetonidine for pediatric sedation forcomputed tomography imaging studies[J].Anesth Analg,2006,103:57-62.
[63]Berkenbosch JW,Wankum PC,Tobias JD.Prospective evaluation of dexmedetonidine fornoninvasive procedural sedation in children[J].Pediatric Crit Care Med,2005,6:435-439.
[64]Talke P, Chen R, Thomas B,et al. The hemodynamic and adrenergic effects ofperioperative dexmedetomidine infusion after vascular surgery. Anesth&Analg2000;90(4):834-839
[65]Yildiz M,Tavlan A,Tunur S,et al.Effect of dexmedetonidine on haemodynamic responsesto laryngoscopy and intubation:perioperative haemodynamics and anaesthetic require-ments[J].Drugs RD,2006,7:43-52.
[66]Maldonado JR，Wysong A，Vander Starre PJA，et al.Dexmedetomidine and the reductionof postoperative delirium after cardiac surgery[J].American Psychiatric Association，2008.
[67]Scheinin B,Lindgren L,Randell T,et al.Dexmedetonidine attenuates sympathoadrenalresponses to tracheal intubation and reduces the need for thiopentone and peroperativefentanyl[J].Br J Anaesth,1992,68:126-131.
[68]Fragen RJ,Fitzgerald PC.Effect of dexmedetonidine on the minimum alveolarconcentration(MAC)of sevoflurane in adults age55to70years[J].J Cline Anesth.1999,11:466-470.
[69]Jaionen J，Hynynen M，Kuitunen A，et al. Dexmedetomidine as an anesthetic adjunct incoronary artery bypass grafting. Anesthesiology,1997;86(2):331-345.
[70]Aho Metal,Aneath Analy,1992;75;940.
[71]Horvaeh R etal,Aneath Analy,1992;74;56.
[72]Scheinim Hetal, Aneatheaiology,1993;78;65.
[1] Monk TG， weldon BC，Garvan CW，et al. predietors of eognitive dysfunction aftermajor non-eardiaesurgery〔J」.Anesthesiology，2008，108(1):18-30.
[2] Steinmetz J， Christensen KB， Rasmussen LS，et al.Long-terme consequenees ofPostoperative eognitive dysfunction{J].Anesthesiolog丛2009.110(3):548-55.。
[3] Dodds C,Allison J.Postoperative cognitive deficit in the elderly surgical patient.Rr JAnaesth,1998;81(3):449.
[4] Newman S P. Analysis and interpretation of neuropsychologic tests in cardiacsurgery[J].Ann Thorac Surg.1995,59(5):1351-1355.
[5] Moler JT，Cluitmans P，Rasmussen LS，et al.Long-term postoperative cognitivedysfunetion in the elderly:ISPOCD1stUdy[J].The Laneet，1998，351:857-861.
[6] Bekker AY,Weeks EJ.Cognitive funetion afteranaesthesia in the elderly[J]Best PraetReClin Anaesthesiol，2003，17:259-72.
[7] Pratico C， Quattrone D， LueantoT,et al.Drugs of anesthesia acting on centralcholinergic system may eause post-operation eognitive dysfunction anddelirium[J].MedHyPothese，2005，65(5):972-982
[8] Parik SS，Chung F.Postoperative delirium in the elderly[J].Anesth Analg，1995，80:1223-32.
[9]王春燕，吴新民。全身麻醉术后对中老年病人认知功能的影目可[J]。中华麻醉学杂志，2002，22(6):332-335.
[10]蔡一榕，薛张刚，朱彪。患者术后认知功能障碍的危险因素分析[J]。临床麻醉学杂志，2006，22(8):608-610.
[11]易善永等,心理行为干预对心脏瓣膜置换术后早期认知功能障碍的影响[J]。中国行为医学科学，2005，6。
[12] Wang Y，Sands LP，VaurioL，et al.The effects of Postoperative Pain and itsmanagement on Postoperative cognitive dysfunctlon[J].Am J Geriati Psyehiatry.2007，15(l):50-59
[13] Cohendy，Robert，Brougere， et al.Anaesthesia in the older Patient[J].Current OPinionin ClinicalNutrit Metabolic Care，2005，8（1）：17-21
[14]李丽萍，江晓，葛衡江。术后疼摘对老年患者术后早期认知功能的影响[J]。重庆医学，2009，38（14）：212-215
[15]张洋等，盐酸右美托咪定的药理作用及其在全身麻醉中的应用。医学临床研究，2011，28（3）
[16] Kanda H，Kurosawa T et al.Effeet of dexlnedetomidine on anesthetic requirements ineardiovaseular sulgery[J].Masui.2009.58(12):1496-1500
[17] Kerdawy H，Gouda N，Kamal H.Dexmedetomidine as anaesthetic adjunet for Patientsundergoing off-PumP coronary artery byPass grafting[J].EgyPtian Joumal ofAnaesthesia，2004.20:29-34
[18]王珊珊，盐酸右美托咪定对高血压患者全麻诱导及气管插管期血流动力学及应激反应的影响[J]。江苏大学，2011
[19]蔡淑女，方军。异丙酚和七氟醚对老年乳腺癌患者术中应激反应和术后认知功能的影响[J]，全科医学临床与教育，2011，02（9）。
[20]朱志华，李龙云，张闻宇。右旋美托咪啶对预防开胸手术患者麻醉苏醒期躁动的临床观察。中国实验诊断学，2011,5。
[21]杨建英，申屠燕琴，裘卫东，吴跃。心率变异性评价盐酸右美托咪定在无痛人流术中的抗焦虑作用[J]。解放军药学，2010,4。