老年患者经鼻蝶入路垂体瘤切除术中应用控制性降压对术后早期认知功能的影响
|
摘要
背景：手术中采用控制性降压技术,可以减少出血,降低了术中输血的需要。同时,出血的减少有效的改善了手术视野。老年人脑血流自动调节功能通常降低,较低血压可能会带来脑组织低灌注的风险。但脑组织的自主调节能力极强。因此,对于老年患者,术中实施控制性降压是否会引起脑损害,以及对术后早期认知功能的影响尚没有确切的结论。
目的：本文旨在观察在经鼻蝶入路垂体瘤切除术中,应用硝普钠控制性降压是否会增加老年患者术后早期认知功能障碍的发生。
方法：选择2012年10月至2013年3月,在山东省立医院手术室,择期行经鼻蝶入路垂体瘤切除术的患者50例。患者均满足以下要求：年龄>60岁,ASAⅠ~Ⅱ级,初中及以上文化程度,凝血功能正常,无明显心、肺、肝和肾功能损害,术前无明确的神经系统或精神疾病史,无酗酒或药物依赖史,既往无手术史,无严重的视力、听力障碍或因其他原因与访视者无法交流。随机均分为C组和CP组。两组行同样的全麻诱导方案,CP组于手术开始后泵注硝普钠行控制性降压,平均动脉压(MAP)下降幅度维持在30%左右,并且MAP不低于60mmHg,术毕停止降压；C组不行控制性降压。术中维持两组患者呼气末二氧化碳分压在正常范围,麻醉用丙泊酚和顺式阿曲库铵维持。术中连续监测心率(H R)、MAP和脉搏血氧饱和度(Sp02)。于术前1天和术后4天,分别用简易精神状态量表MMSE评定两组患者的认知功能。于麻醉前(TO)、术毕(T1)、术毕6小时(T2)和术后24小时(T3)四个时间点,分别抽取外周静脉血3ml,测定S-100β蛋白和神经元特异性烯醇化酶(NSE)含量。
结果：两组患者术后共有5例发生术后认知功能障碍,其中C组2例,发病率8%,CP组3例,发病率12%,组间POCD发生率比较差异无统计学意义(P＞0.05)。组间各时间点的S-100β蛋白和NSE水平比较差异无统计学意义(P＞0.05)。两组患者的术后血清S-100β蛋白和NSE水平均高于术前,差异有统计学意义(P＜0.05)。两组的术后认知功能障碍患者血清S-100β蛋白和NSE含量均高于未发生者,差异有统计学意义(P＜0.05)。
结论：在老年患者经鼻蝶入路垂体瘤手术中,使用硝普钠进行适当的控制性降压,没有增加患者术后早期认知功能障碍的发生率,也没有加重麻醉手术造成的脑损伤。麻醉手术会导致患者术后血清中S-100β蛋白和NSE水平的升高,术后血清中S-100β蛋白和NSE含量的升高可能与术后早期认知功能障碍的发生有关。
BACKGROUND:Recently studies and clinical applications showed that hypotensive anaesthesia could reduce blood loss, which decreased the rate of blood transfusion during operation. At the same time, the reduce of blood loss can also improve surgical field, which provide convenient to operators and reduce operative time. Hypotension may cause hypoperfusion of vital organs. Brain is the most sensitive organ to ischemia and hypoxia. But, brain has a good ability of self-regulation in blood perfusion. So, it is unknown whether controlled hypotension could cause cerebral damage. We also don't understand the effect of controlled hypotension on post-operative cognitive function(POCD).
OBJECTIVE:To observe the effect of controlled hypotension on early cognitive function in elderly patients after transsphenoidal pituitary tumor resection.
METHODS:50patients undergoing transsphenoidal pituitary tumor resection, including33male cases,17female cases, from October2012to March2013, in the operative room of Shandong Provincial Hospital. All patients meet the following requirements:ASA Ⅰ-Ⅱ,junior high school and above degree, normal blood coagulation function, no obvious heart, lung, liver or kidney function damage, no definite neurological or psychiatric history before operation, no alcohol or drug dependence history, no serious vision or hearing barrier or unable to communicate with visitors for other reasons.50patients were randomly divided into group C and group CP. The2groups received the same induction of general anaesthesia, group CP started controlled hypotension by infusion of sodium nitroprusside at the beginning of the operation, the mean arterial pressure (MAP) was decreased about30%, and the MAP is not less than60mmHg,group C did not use controlled hypotension. Maintain the two groups of patients'end-tidal carbon dioxide partial pressure in the normal range during operation, maintain anaesthesia by infusion of propofol and cisatracurium. Continuous monitoring the heart rate(HR), MAP and pulse oxygen saturation (SPO2) in the operation. Assess the cognitive function of all the patients with MMSE, on the day before operation and4days after operation respectively. Extract peripheral venous blood3ml at these4time points:the beginning of anaesthesia (TO), the end of operation (T1),6hours after operation (T2),24hours after operation (T3) and then monitor the content of S-100(3protein and neuron specific enolase (NSE) respectively.
RESULTS:There are total5cases of POCD occurred in the2groups of patients. Group C has2cases with the incidence of8%, and group CP has3cases with the incidence of12%, the incidence of POCD between the groups had no significant difference (P>0.05). There is no statistical significance of S-100β protein and NSE level between the2groups at each time point(P>0.05). The S-100β protein and NSE level of the2groups after operation are both higher than before, the difference is statistically significant (P<0.05). The S-100β protein and NSE level of patients with POCD are significantly higher than the normal(P<0.05).
CONCLUSIONS:It doesn't increase the incidence of POCD and aggravate brain damage, with controlled hypotension by using sodium nitroprusside, during transsphenoidal pituitary tumor resection. Aneasthesia and operation can raise the S-100(3protein and NSE level in patients after operation. The increasing of S-100β protein and NSE content in serum may reflect the occurrence of POCD.
目的：本文旨在观察在经鼻蝶入路垂体瘤切除术中,应用硝普钠控制性降压是否会增加老年患者术后早期认知功能障碍的发生。
方法：选择2012年10月至2013年3月,在山东省立医院手术室,择期行经鼻蝶入路垂体瘤切除术的患者50例。患者均满足以下要求：年龄>60岁,ASAⅠ~Ⅱ级,初中及以上文化程度,凝血功能正常,无明显心、肺、肝和肾功能损害,术前无明确的神经系统或精神疾病史,无酗酒或药物依赖史,既往无手术史,无严重的视力、听力障碍或因其他原因与访视者无法交流。随机均分为C组和CP组。两组行同样的全麻诱导方案,CP组于手术开始后泵注硝普钠行控制性降压,平均动脉压(MAP)下降幅度维持在30%左右,并且MAP不低于60mmHg,术毕停止降压；C组不行控制性降压。术中维持两组患者呼气末二氧化碳分压在正常范围,麻醉用丙泊酚和顺式阿曲库铵维持。术中连续监测心率(H R)、MAP和脉搏血氧饱和度(Sp02)。于术前1天和术后4天,分别用简易精神状态量表MMSE评定两组患者的认知功能。于麻醉前(TO)、术毕(T1)、术毕6小时(T2)和术后24小时(T3)四个时间点,分别抽取外周静脉血3ml,测定S-100β蛋白和神经元特异性烯醇化酶(NSE)含量。
结果：两组患者术后共有5例发生术后认知功能障碍,其中C组2例,发病率8%,CP组3例,发病率12%,组间POCD发生率比较差异无统计学意义(P＞0.05)。组间各时间点的S-100β蛋白和NSE水平比较差异无统计学意义(P＞0.05)。两组患者的术后血清S-100β蛋白和NSE水平均高于术前,差异有统计学意义(P＜0.05)。两组的术后认知功能障碍患者血清S-100β蛋白和NSE含量均高于未发生者,差异有统计学意义(P＜0.05)。
结论：在老年患者经鼻蝶入路垂体瘤手术中,使用硝普钠进行适当的控制性降压,没有增加患者术后早期认知功能障碍的发生率,也没有加重麻醉手术造成的脑损伤。麻醉手术会导致患者术后血清中S-100β蛋白和NSE水平的升高,术后血清中S-100β蛋白和NSE含量的升高可能与术后早期认知功能障碍的发生有关。
BACKGROUND:Recently studies and clinical applications showed that hypotensive anaesthesia could reduce blood loss, which decreased the rate of blood transfusion during operation. At the same time, the reduce of blood loss can also improve surgical field, which provide convenient to operators and reduce operative time. Hypotension may cause hypoperfusion of vital organs. Brain is the most sensitive organ to ischemia and hypoxia. But, brain has a good ability of self-regulation in blood perfusion. So, it is unknown whether controlled hypotension could cause cerebral damage. We also don't understand the effect of controlled hypotension on post-operative cognitive function(POCD).
OBJECTIVE:To observe the effect of controlled hypotension on early cognitive function in elderly patients after transsphenoidal pituitary tumor resection.
METHODS:50patients undergoing transsphenoidal pituitary tumor resection, including33male cases,17female cases, from October2012to March2013, in the operative room of Shandong Provincial Hospital. All patients meet the following requirements:ASA Ⅰ-Ⅱ,junior high school and above degree, normal blood coagulation function, no obvious heart, lung, liver or kidney function damage, no definite neurological or psychiatric history before operation, no alcohol or drug dependence history, no serious vision or hearing barrier or unable to communicate with visitors for other reasons.50patients were randomly divided into group C and group CP. The2groups received the same induction of general anaesthesia, group CP started controlled hypotension by infusion of sodium nitroprusside at the beginning of the operation, the mean arterial pressure (MAP) was decreased about30%, and the MAP is not less than60mmHg,group C did not use controlled hypotension. Maintain the two groups of patients'end-tidal carbon dioxide partial pressure in the normal range during operation, maintain anaesthesia by infusion of propofol and cisatracurium. Continuous monitoring the heart rate(HR), MAP and pulse oxygen saturation (SPO2) in the operation. Assess the cognitive function of all the patients with MMSE, on the day before operation and4days after operation respectively. Extract peripheral venous blood3ml at these4time points:the beginning of anaesthesia (TO), the end of operation (T1),6hours after operation (T2),24hours after operation (T3) and then monitor the content of S-100(3protein and neuron specific enolase (NSE) respectively.
RESULTS:There are total5cases of POCD occurred in the2groups of patients. Group C has2cases with the incidence of8%, and group CP has3cases with the incidence of12%, the incidence of POCD between the groups had no significant difference (P>0.05). There is no statistical significance of S-100β protein and NSE level between the2groups at each time point(P>0.05). The S-100β protein and NSE level of the2groups after operation are both higher than before, the difference is statistically significant (P<0.05). The S-100β protein and NSE level of patients with POCD are significantly higher than the normal(P<0.05).
CONCLUSIONS:It doesn't increase the incidence of POCD and aggravate brain damage, with controlled hypotension by using sodium nitroprusside, during transsphenoidal pituitary tumor resection. Aneasthesia and operation can raise the S-100(3protein and NSE level in patients after operation. The increasing of S-100β protein and NSE content in serum may reflect the occurrence of POCD.
引文
1 Gottesman R F,Hillis A E,Grega M A,et al.Early postoperative cognitive dysfunction and blood pressure during coronary artery by-pass graft operation[J].Arch Neurol,2007,64(8):1111.
2 曹建国,洪涛,闻大翔,等.老年患者术后精神和认知障碍的发病率及相关因素分析.上海医学,2005,28：9392941.
3 Degoute CS. Controlled hypotension:a guide to drug choice [J]. Drugs,2007,67(7):1053-1076.
4 Heyer EJ, Sharma R, Rampersad A, et. al. A controlled prospective study of neuropsychological dysfunction following carotid endarterectomy[J].Arch Neurol, 2002,59(2):217-22.
5 Monk TG, Weldon BC, Garvan CW, et al.Predictors of cognitive dysfunction after major noncardiac surgery[J]..Anesthesiology,2008,108(1):18-30.
6 Dods C. Postoperative cognitive deficit in the elderly surgical patient. Br J Anaesth,1998,81(3):449-462.
7 Evered L, Scott DA, Silbert B, Maruff P. Postoperative cognitive dysfunction is independent of type of surgery and anesthetic. Anesth Analg 2011;112(5):1179-85.
8 Ch oi WS, Samoan N. Risks and benefits of deliberate hypotension in anaesthesia:a systematic review [J]. Int J Oral Maxillofac Surg,2008,37(8) 687-703.
9 Liu X, Zhang JJ. Chronic cerebral Ischemia and cognitive impairment J] Cerebrovasc Dis Forei gn Med Sci,2004,12(4):278.
10 Tomimoto H, Ihar a M, Wakita H, et al. Chronic cerebral hypoperfusion induces white mat ter lesions and loss of oligodendroglia with DNA fragmentation in the rat[J].
11 Kadhim HJ, Duchateau J, Sebire G. Cytokines and brain injury:invited review [J]. J Intensive Care Med,2008,23(4):236-429.
12 Wang CX, Shuaib A. Involvement of inflammatory cytokines in central nervous system injury [J]. Prog Neurobiol,2002,67(2):161-172.
13 Rothennundt M,Peters M, Prehn JH, et al. S-100 β in brain damage and neurodegeneration. MicroseRes"rech.2003,60(6):614-632.
14孙海烽,刘佩蓉,刁枢.尼莫地平对老年手术患者术后认知功能的影响.临床麻醉学杂志。2009,25(3)：237-239.
15 Johnsson P. Markers of cerebral ischemia after cardiac surgery.Cardiothorac Vasc Anesth,1996,10:120-126.
16 Babin-Ebell J,MisophM,MullgesW,et al.Intraoperative embolus formation during cardiopulmonary bypass affects the release of s100B. ThoracCardiovasc Surg, 1999,47(3):166-169.
17 Wilson CA, Finch CE, Cohen I-IJ, et al. Cytokine and cognition-the case for ahead—to-toe inflammatory paradigm. J Am Geriatr Soc,2002,50(12):2041 —56.
18 Godbout JP,Chcn J, Abraham J, et al. Exaggerated neuroinflammation and sickness behavior in aged mice following activation of the peripheral innate immune system. The FASEB Joural. FJ Express,2005,19(7):1329-31.
19 Barrientos RM, Frank MG Hein AM, et al. Time course of hiplxw. ampal Ⅱ,113 and memory consolidation impairments in aged rats following peripheral infection. Brain, Behave and Immune2009,23(1):46-54.
20 Moiler JT,Cluitmans P,Rasmussen LS,er al.Long-term post operative cognitive dysfunction in the elderly.ISPOCD investigators.International study of post-operative cognitive dysfunction[J].Lancet,1998,351 (9106):857-861.
21 Rasmussen LS. Postoperative cognitive dysfunction:incidence and prevention[J]. Best Pract Res Clin Anaesthesiol,2006,20(2):315-330.
1 Steinmetz J,Christensen KB,Lund T,et al,Long-term consequences of postoperative cognitive dysfunction[J].Anesthesiology,2009,110(3):548-555.
2 Saravay SM, Kaplowitz M, Kurek J, et al. How do delirium and dementia increase length of stay of elderly general medical inpatients[J]. Psychosomatics.2004.45(3):235-242.
3 Bourin M, Ripoll N, Da illy E. Nicotinic receptors and Alzheimer's disease[J]. CurrMed ResOpin,2003,19:169-177.
4 Mandal PK, Pettegrew JW, McKeag DW, Mandal R. Alzheimer's disease:halothane induces Abeta peptide to oligomeric form-solution NMR studies.Neurochem Res 2006;31:883-90.
5 Baranov D, Bickler PE, Crosby GJ, et al. Consensus statement:first international workshop on anesthetics and Alzheimer's disease. Anesth Analg,2009;108:1627-30.
6 Mafrica F. Fodale V. Thyroid function, Alzheimer's disease and postoperative cognitive dysfunction:A tale of dangerous liais on[j]. Alzheimer's Disease,2008。14(1):95-105.
7 Monk TG,Weldon BC,Garvan CW,er al.Predictors of cognitive dysfunction after major noncardiac surgery.Anesthesiology,2008,108(1):18-30.
8 Culley DJ, Baxter MG, Yukhananov R, Crosby G. Long-term impairment of acquisition of a spatial memory task following isoflurane-nitrous oxide anesthesia in rats. Anesthesiology 2004; 100:309-14.
9 Cibelli M,Fidalgo AR,Terrando N,er al.Role of interlerkin-1beta in postoperative cognitive dysfunction.Ann Neurol,2010,68(3):360-368.
10 Rohm KD, Piper SN, Suttner S, Schuler S, Boldt J. Early recovery, cognitive function and costs of a desflurane inhalational vs a total intravenous anaesthesia regimen in long-term surgery.. Acta Anaesthesiol Scand,2006:50:14-8.
11 Fillenbaum GG. Landerman LR, Blazer DG,et al. The relationship of ApoE genotype to cognitive functioning in older African—American and Caucasian community residents[J]. j Am Geriatr Soc,2001,49:1148—1155.
12 Farag E, Chelune GJ, Schubert A, Mascha EJ. Is depth of anesthesia, as assessed by the bispectral index, related to postoperative cognitive dysfunction and recovery? Anesth Analg,2006;103:633-40.
13 Rohm KD, Piper SN, Suttner S, Schuler S, Boldt J. Early recovery, cognitive function and costs of a desflurane inhalational vs a total intravenous anaesthesia regimen in long-term surgery.. Acta Anaesthesiol Scand,2006;50:14-8.
14 Xie,Z.,Romano,D.M.,Tanzi,R.E.,2005b.RNA interference-mediated silencing of X11 alpha and X11beta attenuates amyloid beta-protein levels via differential effects on beta-amyloid precursor protein processing. J. Biol.Chem,280, 15413-15421.
15 Xie, Z., Romano, D.M., Tanzi, R.E.,2005a. Effects of RNAi-mediated silencing of PEN-2, APH-1a, and nicastrin on wild-type vs FAD mutant forms of presenilin 1. J. Mol. Neurosci.25,67-77.
16 Tanzi, R.E.,2005a. The synaptic Abeta hypothesis of Alzheimer disease. Nat. Neurosci.8,977-979.
17 Cleary, J.P., Walsh, D.M., Hofmeister, J.J., Shankar, G.M.,Kuskowski, M.A., Selkoe, D.J.,Ashe, K.H.,2005. Natural oligomers of the amyloid-beta protein specifically disrupt cognitive function. Nat.Neurosci.8,79-84.
18 Tanzi, R.E., Bertram, L.,2005. Twenty years of the Alzheimer's disease amyloid hypothesis:a genetic perspective. Cell 120,545-555.
19 Poirier, J.,2000. Apolipoprotein E and Alzheimer's disease. A role in amyloid catabolism. Ann. NY Acad. Sci.924,81-90.
20 Tanzi, R.E., Moir, R.D., Wagner, S.L.,2004. Clearance of Alzheimer's Abeta peptide:the many roads to perdition. Neuron 43,605-608.
21 Blacker, D., Bertram, L., Saunders, A.J., Moscarillo, T.J., Albert, M.S.,Wiener, H..Perry,R.T., Collins, J.S., Harrell, L.E., Go, R.C., et al.,2003.Results of a high-resolution genome screen of 437 Alzheimer's disease families. Hum. Mol. Genet. 12,23-32.
22Bennett,D.A.,Schneider,J.A.,Wilson,R.S.,Bienias,J.L.,Arnold,S.E.,2004.Neuro fibrillary tangles mediate the association of amyloid load with clinical Alzheimer disease and level of cognitive function. Arch. Neurol.61,378-384.
23 Santacruz, K., Lewis, J., Spires, T., Paulson, J., Kotilinek, L., Ingelsson, M.,Guimaraes, A., DeTure, M., Ramsden, M., McGowan, E., et al.,2005. Tau suppression in a neurodegenerative mouse model improves memory function. Science 309,476-481.
24 Kawaguchi, M., Drummond, J.C., Cole, D.J., Kelly, P.J., Spurlock, M.P.,Patel, P.M.,2004. Effect of isoflurane on neuronal apoptosis in rats subjected to focal cerebral ischemia. Anesth. Analg.98,798-805 (table of contents).
25 Gray, J.J., Bickler, P.E., Fahlman, C.S., Zhan, X., Schuyler, J.A., 2005.Isoflurane neuroprotection in hypoxic hippocampal slice cultures involves increases in intracellular Ca2+ and mitogen-activated protein kinases.Anesthesiology 102,606-615.
26 Kvolik, S., Glavas-Obrovac, L., Bares, V., Karner, I.,2005. Effects of inhalation anesthetics halothane, sevoflurane, and isoflurane on human cell lines. Life Sci.77,2369-2383.
27 Culley, D.J., Baxter, M.G., Yukhananov, R., Crosby, G.,2004. Long-term impairment of acquisition of a spatial memory task following isofluranenitrous oxide anesthesia in rats. Anesthesiology 100,309-314.
28 Wise-Faberowski, L., Aono, M., Pearlstein, R.D., Warner, D.S., 2004.Apoptosis is not enhanced in primary mixed neuronal/glial cultures protected by isoflurane against N-methyl-D-aspartate excitotoxicity.Anesth. Analg.99, 1708-1714
29 Eckenhoff, R.G., Johansson, J.S., Wei, H., Carnini, A., Kang, B., Wei, W.,Pidikiti, R.,Keller, J.M., Eckenhoff, M.F.,2004. Inhaled anesthetic enhancement of amyloid-beta oligomerization and cytotoxicity. Anesthesiology.101,703-709.
30 Kokmen, E., Whisnant, J.P., O'Fallon, W.M., Chu, C.P., Beard, C.M.,1996. Dementia after ischemic stroke:a population-based study in Rochester, Minnesota (1960-1984). Neurology 46,154-159.
31 Snowdon, D.A., Greiner, L.H., Mortimer, J.A., Riley, K.P., Greiner, P.A., Markesbery,W.R.,1997. Brain infarction and the clinical expression of Alzheimer disease. The Nun Study. JAMA 277,813-817.
32 Kokmen, E., Whisnant, J.P., O'Fallon, W.M., Chu, C.P., Beard, C.M.,1996. Dementia after ischemic stroke:a population-based study in Rochester,Minnesota (1960-1984). Neurology 46,154-159.
33 Chen, G.J., Xu, J., Lahousse, S.A., Caggiano, N.L., de la Monte, S.M., 2003.Transient hypoxia causes Alzheimer-type molecular and biochemical abnormalities in cortical neurons:potential strategies for neuroprotection.J. Alzheimers Dis.5,209-228.
34 Dodds, C., Allison, J.,1998. Postoperative cognitive deficit in the elderly surgical patient. Br. J. Anaesth.81,449-462.
35 Ohyu, J., Endo, A., Itoh, M., Takashima, S.,2000. Hypocapnia under hypotension induces apoptotic neuronal cell death in the hippocampus of newborn rabbits. Pediatr. Res.48,24-29.
36 Xie, Z., Moir, R., Romano, D.M., Tesco, G., Kovacs, D., Tanzi, R.E., 2004a.Hypocapnia induces caspase-3 activation and increases A-beta production.Neurodegenerative Dis.1,29-37.
37 Xie, Z., Dong, Y., Maeda, U., Alfille, P., Culley, DJ., Crosby, G., Tanzi, RE., in press.The common inhalation anesthetic isoflurane induces apoptosis and increases amyloid beta-protein levels. Anesthesiology.
38 Culley DJ, Baxter MG, Yukhananov R, Crosby G. Long-term impairment of acquisition of a spatial memory task following isoflurane-nitrous oxide anesthesia in rats. Anesthesiology 2004; 100:309-14.
39 Rohm KD, Piper SN, Suttner S, Schuler S, Boldt J. Early recovery, cognitive function and costs of a desflurane inhalational vs a total intravenous anaesthesia regimen in long-term surgery.. Acta Anaesthesiol Scand,2006;50:14-8.
40 Farag E, Chelune GJ, Schubert A, Mascha EJ. Is depth of anesthesia, as assessed by the bispectral index, related to postoperative cognitive dysfunction and recovery? Anesth Analg,2006; 103:633-40.
41 Rasmussen LS, Johnson T, Kuipers HM, et al. Does anesthesia cause postoperative cognitive dysfunction? A randomised study of regional versus general anesthesia in 438 elderly patients.Acta Anesthesiol Scand,2003;47:260-6.
42 Sheeran P, Hall GM. Cytokines in anaesthesia. Br J Anaesth 1997;78:201-19.
43 Wilson CJ, Finch CE, Cohen HJ. Cytokines and cognition-the case for a headto-toe inflammatory paradigm. J Am Geriatr Soc 2002;50:2041-56.
44 Yong VW, Krekoski CA, Forsyth PA, Bell R, Edwards DR. Matrix metalloproteinases and diseases of the CNS. Trends Neurosci 1998;21:75-80.
45 Ramlawi B, Rudolph JL, Mieno S, et al. C-Reactive protein and inflammatory response associated to neurocognitive decline following cardiac surgery. Surgery 2006;140:221-6.
46 Minagar A, Shapshak P, Fujimura R, Ownby R, Heyes M, Eisdorfer C. The role of macrophage/microglia and astrocytes in the pathogenesis of three neurologic disorders:HIV-associated dementia, Alzheimer disease, and multiple sclerosis.J Neurol Sci 2002;202:13-23.
47 Wan Y, Xu J, Ma D, Zeng Y, Cibelli M, Maze M. Postoperative impairment of cognitive function in rats:a possible role for cytokine-mediated inflammation in the hippocampus. Anesthesiology 2007; 106:436-43.
48 Kalman J, Juhasz A, Bogats G, et al. Elevated levels of inflammatory biomarkers in the cerebrospinal fluid after coronary artery bypass surgery are predictors of cognitive decline. Neurochem Int 2006;48:177-80.
49 Guerreiro RJ, Santana I, Bras JM, Santiago B, Paiva A, Oliveira C. Peripheral inflammatory cytokines as biomarkers in Alzheimer's disease and mild cognitive impairment. Neurodegener Dis,2007;4:406-12.
50 Vehmas AK, Kawas CH, Stewart WF, Troncoso JC. Immune reactive cells in senile plaques and cognitive decline in Alzheimer's disease. Neurobiol Aging,2003;24:321-31.
51 Mrak RE, Griffin WS. Interleukin-1, neuroinflammation, and Alzheimer's disease. Neurobiol Aging 2001;22:903-8.
2 曹建国,洪涛,闻大翔,等.老年患者术后精神和认知障碍的发病率及相关因素分析.上海医学,2005,28：9392941.
3 Degoute CS. Controlled hypotension:a guide to drug choice [J]. Drugs,2007,67(7):1053-1076.
4 Heyer EJ, Sharma R, Rampersad A, et. al. A controlled prospective study of neuropsychological dysfunction following carotid endarterectomy[J].Arch Neurol, 2002,59(2):217-22.
5 Monk TG, Weldon BC, Garvan CW, et al.Predictors of cognitive dysfunction after major noncardiac surgery[J]..Anesthesiology,2008,108(1):18-30.
6 Dods C. Postoperative cognitive deficit in the elderly surgical patient. Br J Anaesth,1998,81(3):449-462.
7 Evered L, Scott DA, Silbert B, Maruff P. Postoperative cognitive dysfunction is independent of type of surgery and anesthetic. Anesth Analg 2011;112(5):1179-85.
8 Ch oi WS, Samoan N. Risks and benefits of deliberate hypotension in anaesthesia:a systematic review [J]. Int J Oral Maxillofac Surg,2008,37(8) 687-703.
9 Liu X, Zhang JJ. Chronic cerebral Ischemia and cognitive impairment J] Cerebrovasc Dis Forei gn Med Sci,2004,12(4):278.
10 Tomimoto H, Ihar a M, Wakita H, et al. Chronic cerebral hypoperfusion induces white mat ter lesions and loss of oligodendroglia with DNA fragmentation in the rat[J].
11 Kadhim HJ, Duchateau J, Sebire G. Cytokines and brain injury:invited review [J]. J Intensive Care Med,2008,23(4):236-429.
12 Wang CX, Shuaib A. Involvement of inflammatory cytokines in central nervous system injury [J]. Prog Neurobiol,2002,67(2):161-172.
13 Rothennundt M,Peters M, Prehn JH, et al. S-100 β in brain damage and neurodegeneration. MicroseRes"rech.2003,60(6):614-632.
14孙海烽,刘佩蓉,刁枢.尼莫地平对老年手术患者术后认知功能的影响.临床麻醉学杂志。2009,25(3)：237-239.
15 Johnsson P. Markers of cerebral ischemia after cardiac surgery.Cardiothorac Vasc Anesth,1996,10:120-126.
16 Babin-Ebell J,MisophM,MullgesW,et al.Intraoperative embolus formation during cardiopulmonary bypass affects the release of s100B. ThoracCardiovasc Surg, 1999,47(3):166-169.
17 Wilson CA, Finch CE, Cohen I-IJ, et al. Cytokine and cognition-the case for ahead—to-toe inflammatory paradigm. J Am Geriatr Soc,2002,50(12):2041 —56.
18 Godbout JP,Chcn J, Abraham J, et al. Exaggerated neuroinflammation and sickness behavior in aged mice following activation of the peripheral innate immune system. The FASEB Joural. FJ Express,2005,19(7):1329-31.
19 Barrientos RM, Frank MG Hein AM, et al. Time course of hiplxw. ampal Ⅱ,113 and memory consolidation impairments in aged rats following peripheral infection. Brain, Behave and Immune2009,23(1):46-54.
20 Moiler JT,Cluitmans P,Rasmussen LS,er al.Long-term post operative cognitive dysfunction in the elderly.ISPOCD investigators.International study of post-operative cognitive dysfunction[J].Lancet,1998,351 (9106):857-861.
21 Rasmussen LS. Postoperative cognitive dysfunction:incidence and prevention[J]. Best Pract Res Clin Anaesthesiol,2006,20(2):315-330.
1 Steinmetz J,Christensen KB,Lund T,et al,Long-term consequences of postoperative cognitive dysfunction[J].Anesthesiology,2009,110(3):548-555.
2 Saravay SM, Kaplowitz M, Kurek J, et al. How do delirium and dementia increase length of stay of elderly general medical inpatients[J]. Psychosomatics.2004.45(3):235-242.
3 Bourin M, Ripoll N, Da illy E. Nicotinic receptors and Alzheimer's disease[J]. CurrMed ResOpin,2003,19:169-177.
4 Mandal PK, Pettegrew JW, McKeag DW, Mandal R. Alzheimer's disease:halothane induces Abeta peptide to oligomeric form-solution NMR studies.Neurochem Res 2006;31:883-90.
5 Baranov D, Bickler PE, Crosby GJ, et al. Consensus statement:first international workshop on anesthetics and Alzheimer's disease. Anesth Analg,2009;108:1627-30.
6 Mafrica F. Fodale V. Thyroid function, Alzheimer's disease and postoperative cognitive dysfunction:A tale of dangerous liais on[j]. Alzheimer's Disease,2008。14(1):95-105.
7 Monk TG,Weldon BC,Garvan CW,er al.Predictors of cognitive dysfunction after major noncardiac surgery.Anesthesiology,2008,108(1):18-30.
8 Culley DJ, Baxter MG, Yukhananov R, Crosby G. Long-term impairment of acquisition of a spatial memory task following isoflurane-nitrous oxide anesthesia in rats. Anesthesiology 2004; 100:309-14.
9 Cibelli M,Fidalgo AR,Terrando N,er al.Role of interlerkin-1beta in postoperative cognitive dysfunction.Ann Neurol,2010,68(3):360-368.
10 Rohm KD, Piper SN, Suttner S, Schuler S, Boldt J. Early recovery, cognitive function and costs of a desflurane inhalational vs a total intravenous anaesthesia regimen in long-term surgery.. Acta Anaesthesiol Scand,2006:50:14-8.
11 Fillenbaum GG. Landerman LR, Blazer DG,et al. The relationship of ApoE genotype to cognitive functioning in older African—American and Caucasian community residents[J]. j Am Geriatr Soc,2001,49:1148—1155.
12 Farag E, Chelune GJ, Schubert A, Mascha EJ. Is depth of anesthesia, as assessed by the bispectral index, related to postoperative cognitive dysfunction and recovery? Anesth Analg,2006;103:633-40.
13 Rohm KD, Piper SN, Suttner S, Schuler S, Boldt J. Early recovery, cognitive function and costs of a desflurane inhalational vs a total intravenous anaesthesia regimen in long-term surgery.. Acta Anaesthesiol Scand,2006;50:14-8.
14 Xie,Z.,Romano,D.M.,Tanzi,R.E.,2005b.RNA interference-mediated silencing of X11 alpha and X11beta attenuates amyloid beta-protein levels via differential effects on beta-amyloid precursor protein processing. J. Biol.Chem,280, 15413-15421.
15 Xie, Z., Romano, D.M., Tanzi, R.E.,2005a. Effects of RNAi-mediated silencing of PEN-2, APH-1a, and nicastrin on wild-type vs FAD mutant forms of presenilin 1. J. Mol. Neurosci.25,67-77.
16 Tanzi, R.E.,2005a. The synaptic Abeta hypothesis of Alzheimer disease. Nat. Neurosci.8,977-979.
17 Cleary, J.P., Walsh, D.M., Hofmeister, J.J., Shankar, G.M.,Kuskowski, M.A., Selkoe, D.J.,Ashe, K.H.,2005. Natural oligomers of the amyloid-beta protein specifically disrupt cognitive function. Nat.Neurosci.8,79-84.
18 Tanzi, R.E., Bertram, L.,2005. Twenty years of the Alzheimer's disease amyloid hypothesis:a genetic perspective. Cell 120,545-555.
19 Poirier, J.,2000. Apolipoprotein E and Alzheimer's disease. A role in amyloid catabolism. Ann. NY Acad. Sci.924,81-90.
20 Tanzi, R.E., Moir, R.D., Wagner, S.L.,2004. Clearance of Alzheimer's Abeta peptide:the many roads to perdition. Neuron 43,605-608.
21 Blacker, D., Bertram, L., Saunders, A.J., Moscarillo, T.J., Albert, M.S.,Wiener, H..Perry,R.T., Collins, J.S., Harrell, L.E., Go, R.C., et al.,2003.Results of a high-resolution genome screen of 437 Alzheimer's disease families. Hum. Mol. Genet. 12,23-32.
22Bennett,D.A.,Schneider,J.A.,Wilson,R.S.,Bienias,J.L.,Arnold,S.E.,2004.Neuro fibrillary tangles mediate the association of amyloid load with clinical Alzheimer disease and level of cognitive function. Arch. Neurol.61,378-384.
23 Santacruz, K., Lewis, J., Spires, T., Paulson, J., Kotilinek, L., Ingelsson, M.,Guimaraes, A., DeTure, M., Ramsden, M., McGowan, E., et al.,2005. Tau suppression in a neurodegenerative mouse model improves memory function. Science 309,476-481.
24 Kawaguchi, M., Drummond, J.C., Cole, D.J., Kelly, P.J., Spurlock, M.P.,Patel, P.M.,2004. Effect of isoflurane on neuronal apoptosis in rats subjected to focal cerebral ischemia. Anesth. Analg.98,798-805 (table of contents).
25 Gray, J.J., Bickler, P.E., Fahlman, C.S., Zhan, X., Schuyler, J.A., 2005.Isoflurane neuroprotection in hypoxic hippocampal slice cultures involves increases in intracellular Ca2+ and mitogen-activated protein kinases.Anesthesiology 102,606-615.
26 Kvolik, S., Glavas-Obrovac, L., Bares, V., Karner, I.,2005. Effects of inhalation anesthetics halothane, sevoflurane, and isoflurane on human cell lines. Life Sci.77,2369-2383.
27 Culley, D.J., Baxter, M.G., Yukhananov, R., Crosby, G.,2004. Long-term impairment of acquisition of a spatial memory task following isofluranenitrous oxide anesthesia in rats. Anesthesiology 100,309-314.
28 Wise-Faberowski, L., Aono, M., Pearlstein, R.D., Warner, D.S., 2004.Apoptosis is not enhanced in primary mixed neuronal/glial cultures protected by isoflurane against N-methyl-D-aspartate excitotoxicity.Anesth. Analg.99, 1708-1714
29 Eckenhoff, R.G., Johansson, J.S., Wei, H., Carnini, A., Kang, B., Wei, W.,Pidikiti, R.,Keller, J.M., Eckenhoff, M.F.,2004. Inhaled anesthetic enhancement of amyloid-beta oligomerization and cytotoxicity. Anesthesiology.101,703-709.
30 Kokmen, E., Whisnant, J.P., O'Fallon, W.M., Chu, C.P., Beard, C.M.,1996. Dementia after ischemic stroke:a population-based study in Rochester, Minnesota (1960-1984). Neurology 46,154-159.
31 Snowdon, D.A., Greiner, L.H., Mortimer, J.A., Riley, K.P., Greiner, P.A., Markesbery,W.R.,1997. Brain infarction and the clinical expression of Alzheimer disease. The Nun Study. JAMA 277,813-817.
32 Kokmen, E., Whisnant, J.P., O'Fallon, W.M., Chu, C.P., Beard, C.M.,1996. Dementia after ischemic stroke:a population-based study in Rochester,Minnesota (1960-1984). Neurology 46,154-159.
33 Chen, G.J., Xu, J., Lahousse, S.A., Caggiano, N.L., de la Monte, S.M., 2003.Transient hypoxia causes Alzheimer-type molecular and biochemical abnormalities in cortical neurons:potential strategies for neuroprotection.J. Alzheimers Dis.5,209-228.
34 Dodds, C., Allison, J.,1998. Postoperative cognitive deficit in the elderly surgical patient. Br. J. Anaesth.81,449-462.
35 Ohyu, J., Endo, A., Itoh, M., Takashima, S.,2000. Hypocapnia under hypotension induces apoptotic neuronal cell death in the hippocampus of newborn rabbits. Pediatr. Res.48,24-29.
36 Xie, Z., Moir, R., Romano, D.M., Tesco, G., Kovacs, D., Tanzi, R.E., 2004a.Hypocapnia induces caspase-3 activation and increases A-beta production.Neurodegenerative Dis.1,29-37.
37 Xie, Z., Dong, Y., Maeda, U., Alfille, P., Culley, DJ., Crosby, G., Tanzi, RE., in press.The common inhalation anesthetic isoflurane induces apoptosis and increases amyloid beta-protein levels. Anesthesiology.
38 Culley DJ, Baxter MG, Yukhananov R, Crosby G. Long-term impairment of acquisition of a spatial memory task following isoflurane-nitrous oxide anesthesia in rats. Anesthesiology 2004; 100:309-14.
39 Rohm KD, Piper SN, Suttner S, Schuler S, Boldt J. Early recovery, cognitive function and costs of a desflurane inhalational vs a total intravenous anaesthesia regimen in long-term surgery.. Acta Anaesthesiol Scand,2006;50:14-8.
40 Farag E, Chelune GJ, Schubert A, Mascha EJ. Is depth of anesthesia, as assessed by the bispectral index, related to postoperative cognitive dysfunction and recovery? Anesth Analg,2006; 103:633-40.
41 Rasmussen LS, Johnson T, Kuipers HM, et al. Does anesthesia cause postoperative cognitive dysfunction? A randomised study of regional versus general anesthesia in 438 elderly patients.Acta Anesthesiol Scand,2003;47:260-6.
42 Sheeran P, Hall GM. Cytokines in anaesthesia. Br J Anaesth 1997;78:201-19.
43 Wilson CJ, Finch CE, Cohen HJ. Cytokines and cognition-the case for a headto-toe inflammatory paradigm. J Am Geriatr Soc 2002;50:2041-56.
44 Yong VW, Krekoski CA, Forsyth PA, Bell R, Edwards DR. Matrix metalloproteinases and diseases of the CNS. Trends Neurosci 1998;21:75-80.
45 Ramlawi B, Rudolph JL, Mieno S, et al. C-Reactive protein and inflammatory response associated to neurocognitive decline following cardiac surgery. Surgery 2006;140:221-6.
46 Minagar A, Shapshak P, Fujimura R, Ownby R, Heyes M, Eisdorfer C. The role of macrophage/microglia and astrocytes in the pathogenesis of three neurologic disorders:HIV-associated dementia, Alzheimer disease, and multiple sclerosis.J Neurol Sci 2002;202:13-23.
47 Wan Y, Xu J, Ma D, Zeng Y, Cibelli M, Maze M. Postoperative impairment of cognitive function in rats:a possible role for cytokine-mediated inflammation in the hippocampus. Anesthesiology 2007; 106:436-43.
48 Kalman J, Juhasz A, Bogats G, et al. Elevated levels of inflammatory biomarkers in the cerebrospinal fluid after coronary artery bypass surgery are predictors of cognitive decline. Neurochem Int 2006;48:177-80.
49 Guerreiro RJ, Santana I, Bras JM, Santiago B, Paiva A, Oliveira C. Peripheral inflammatory cytokines as biomarkers in Alzheimer's disease and mild cognitive impairment. Neurodegener Dis,2007;4:406-12.
50 Vehmas AK, Kawas CH, Stewart WF, Troncoso JC. Immune reactive cells in senile plaques and cognitive decline in Alzheimer's disease. Neurobiol Aging,2003;24:321-31.
51 Mrak RE, Griffin WS. Interleukin-1, neuroinflammation, and Alzheimer's disease. Neurobiol Aging 2001;22:903-8.