1、急性stanford-A型主动脉夹层围术期流行病学现状 急性A型主动脉夹层的发病率 急性主动脉急性主动脉A型型夹层（夹层（Acute type A aortic dissection）的发病率约为每年5-30/100万（美国，2000年）P.G.Hagan,C.A.Nienaber,E.M.Isselbacher et al.,“The International Registry of Acute Aortic Dissection(IRAD):new insights into an old disease,”Journal of the American Medical Associat
2、ion,vol.283,no.7,pp.897903,2000.。临床资料表明，此类病人如不进行治疗发病病死率病死率可达30，并且以以1小时增加小时增加1-2的速度发展的速度发展，48小时内的死亡率可达68，1个月内的死亡率可达90。I.Mszros,J.Mrocz,J.Szlvi et al.,“Epidemiology and clinicopathology of aortic dissection:a population-based longitudinal study over 27 years,”Chest,vol.117,no.5,pp.12711278,2000.C.A.Ni
3、enaber and K.A.Eagle,“Aortic dissection:new frontiers in diagnosis and management.Part I:from etiology to diagnostic strategies,”Circulation,vol.108,no.5,pp.628635,2003.流行病学现状急性 A型夹层致急性肺损伤（ALI）发生率 急性stanford A型主动脉夹层术前不同程度肺损伤发生率可达50-80%，术后严重肺损伤发生率约8-30%，约占总体死亡率40%Sugano Y,Anzai T,Yoshikawa T,et al.Se
4、rum C-reactive protein elevation predicts poor clinical outcome in patients with distal type acute aortic dissection:association with the occurrence of oxygenation impairment.Int J Cardiol 2005;102(1):3945Yinghua Wang*,Song Xue and Hongsheng Zhu.Risk factors for postoperative hypoxemia in patients u
5、ndergoing Stanford A aortic dissection surgery.Journal of Cardiothoracic Surgery 2013,8:118我院资料：Patients with acute TAAD had a greater incidence of operative death(8.1%vs 4.3%;P=.031),and respiratory morbidities(20.8%vs 8.6%;P .001).（N=803）SUN LZ.etal.Frozen elephant trunk with total arch replacemen
6、t for type A aortic dissections:Does acuity affect operative mortality?J Thorac Cardiovasc Surg.2014 Sep;148(3):963-72.ALI发病的危险因素ALI发病的危险因素（术前）Kazunori Tomita,MD.etal.Predicting the Occurrence of Oxygenation Impairment in Patients with Type-B Acute Aortic Dissection.Int J Angiol 2014;23:5360.79 B型急性
7、夹层（发病时间小于24小时）氧合不良：PO2/FIO2 200 mmHg.发生率：39 例(49%)发生时间：入院2.5 1.4 天ALI发病的危险因素（术前）Kazunori Tomita,MD.etal.Predicting the Occurrence of Oxygenation Impairment in Patients with Type-B Acute Aortic Dissection.Int J Angiol 2014;23:5360.ALI发病的危险因素（术前）Manabu Kurabayashi,MD.etal.Reduction of the PaO2/FiO2 Ra
8、tio in Acute Aortic Dissection Relationship Between the Extent of Dissection and Inflammation Circ J 2010;74:2066207349 例远端急性夹层动脉瘤氧合不良：PaO2/FiO2 ratio 200.发生率：19 例(39%)危险因素AAD%(50.810.9%vs 28.011.9%,P0.001),峰值 CRP(15.26.5 mg/dl vs 9.64.6 mg/dl,P0.001),峰值 WBC(13,6003,700/l vs 10,4002,800/l,P=0.001)体温
9、(38.10.5C vs 37.80.4C,P=0.045)多因素分析AAD%是术前氧合不良的独立危险因素ALI发病的危险因素（术前）首都卫生发展科研专项(2011-2006-03)。国际临床试验注册号：ClinicalTrails(WCheng)2012-2014年安贞医院130例急性stanford A型主动脉夹层ALI定义：PaO2/FiO2300mmHg，结合呼吸动力学指标55%（71例）有不同程度的肺损伤ALI发病的危险因素（术前）VariablesBS.E.WalddfSig.Exp(B)95%CIfor EXP(B)LowerUpperAGE0.1280.03513.41010.
10、0001.1371.0611.218BMI0.2200.0935.60010.0181.2461.0391.495Preoperative DBP-0.0460.0224.33910.0370.9550.9140.997IL-60.0270.0125.26710.0221.0271.0041.051TFPI-0.0090.0044.35510.0370.9910.9830.999PGI2/TXB2 ratio-1.3240.4508.67510.0030.2660.1100.642Constant-8.3343.5645.46810.0190.000Multiple logistic regr
11、ession analysis for preoperative ALIALI发病的危险因素（术后）Evaldas Girdauskas.et.al.Acute respiratory dysfunction after surgery for acute type A aortic dissection.European Journal of Cardio-thoracic Surgery 37(2010)6916961994-2008 276例急性A型夹层术后氧合不良：PaO2/FiO2 150发生率37 例(13%).Malperfusion是术后氧合不良的危险因素.ALI发病的危险因素
12、（术后）Yinghua Wang*,Song Xue and Hongsheng Zhu.Risk factors for postoperative hypoxemia in patients undergoing Stanford A aortic dissection surgery.Journal of Cardiothoracic Surgery 2013,8:1182004-2012,186 例急性A型夹层.氧合不良：PaO2/FiO2 200 mmHg发生率49.5%.危险因素急性起病 (p=0.000),术前 PaO2/FiO2)200 mmHg(p=0.000),体重指数(p
13、=0.008),停循环时间(CA)time(p=0.000)输血大于 3000 ml(p=0.000).ALI发病的危险因素（术后）Sheng W1,Yang HQ,Chi YF,Niu ZZ,Lin MS,Long S.Independent risk factors for hypoxemia after surgery for acute aortic dissection.Saudi Med J.2015 Aug;36(8):940-6.2007-2013,192 例急性A型夹层.氧合不良：PaO2/FiO2 200 mmHg发生率28.6%.ALI发病机制ALI发病机制（术前凝血）图
14、3 53例急性主动脉夹层循环TF（组织因子）与氧合指数相关性呈负相关性(r-0.622，P0.01)，图4 53例急性主动脉夹层肺泡灌洗液TF与氧合指数相关性呈负相关(r=-0.571，P0.01)首都卫生发展科研专项(2011-2006-03)。国际临床试验注册号：ClinicalTrails(WCheng)ALI发病机制（术前凝血）诱导后高岭土诱导后高岭土角角诱导后高岭土诱导后高岭土MA无肺损伤组 n=4866.72.566.61.5肺损伤组 n=4458.11.662.11.3P值0.050.05凝血功能下降ALI发病机制（术前凝血）Coagulation NO-ALI（N=60)ALI
15、 (N=70）PAPTT(s)30.5(28.9,32.1)30.3(28.4,32.3)0.669PT(s)12.3(11.7,12.9)12.5(11.7,13.5)0.263PAI1(ng/mL)0.700.210.720.190.561TF(ng/mL)4.162.623.972.550.694TFPI(pg/mL)16378132580.016TFPI：组织因子途径抑制物，是控制凝血启动阶段的一种体内天然抗凝蛋白，它对组织因子途径（即外源性凝血途径）具有特异性抑制作用，曾称为外在途径抑制物主要来源于血管内皮细胞。ALI发病机制（术前纤溶）2012年10月至2013年12月北京安贞医院
16、符合条件的ADD患者共53例，根据术前是否发生ALI分为术前ALI组（A组，22例）组和术前非ALI组（C组，31例）。PaO2/FiO2300mmHg首都卫生发展科研专项(2011-2006-03)。国际临床试验注册号：ClinicalTrails(WCheng)ALI发病机制（术前纤溶）图5 53例急性主动脉夹层循环PAI-1（纤溶酶原激活物抑制剂）与氧合指数相关性呈负相关性(r-0.504 P0.01)，图6 53例急性主动脉夹层肺泡灌洗液PAI-1与氧合指数相关性呈负相关(r=-0.606，P0.01)首都卫生发展科研专项(2011-2006-03)。国际临床试验注册号：Clinica
17、lTrails(WCheng)ALI发病机制（术前纤溶）术前高岭土术前高岭土EPL术前高岭土术前高岭土LY30无肺损伤组 n=480.680.120.650.10肺损伤组 n=441.240.161.190.12P值0.050.05纤溶抗进ALI发病机制（术前炎症）Serum Variables before surgeryNO-ALI（N=60)ALI (N=70）PInflammatoryIL-6(pg/mL)57.121.265.925.60.042IL-10(pg/mL)100.268.878.850.40.050HLE(ng/mL)2.341.612.381.090.854TNF(p
18、g/mL)63.238.853.324.60.092炎症反应增强ALI发病机制（术前血小板和内皮细胞）Serum Variables before surgeryNO-ALI（N=60)ALI (N=70）PPlatelet and endothelial cellPLC(109/L)19069168700.087VEGF(pg/mL)196(129,381)191(134,505)0.883PGI2(pg/mL)38.4(21.4,131.8)41.8(23.8,82.5)0.915TXB2(pg/mL)99.6(77.5,162.9)144.5(86.5,208.6)0.044PGI2/T
19、XB2 ratio0.36(0.21,1.2)0.28(0.17,0.62)0.068急性A型夹层导致ALI的治疗进展 药物 体外循环方法和技术的改进 肺动脉灌注 保护性肺通气策略药物（早期干预）Jo Y1,Anzai T.etal.Early use of beta-blockers attenuates systemic inflammatory response and lung oxygenation impairment after distal type acute aortic dissection.Heart Vessels.2008 Sep;23(5):334-4049 例远
20、端急性夹层40例在发病24小时内给予受体阻断剂结果降低白细胞计数的峰值(P=0.0028)降低C反应蛋白的峰值(P=0.0004).改善呼吸指数(P=0.0076).多因素分析受体阻断剂是独立保护因素(呼吸指数 or=200 mmHg).药物（早期干预）Shingu Y1,Shiiya N,Matsuzaki K,Kunihara T,Murashita T,Matsui Y.Effect of sivelestat sodium on acute lung injury after acute aortic dissection Kyobu Geka.2008 Jun;61(6):440-3
21、.11 patients with AAD in which sivelestat（弹性蛋白酶抑制药）was used prophylacticaly 12 patients（control group）结果对照组5例（42%）需机械通气用药组无需机械通气病例26对围术期氧合指数影响术后呼吸机治疗术后呼吸机治疗时间时间 17h(15,56)vs 16.5h(14,67)27乌司他丁早期干预可以有效减轻ADD术后炎性反应（0=对照组,n=40；1=乌司他丁组,n=40）28乌司他丁早期干预可以有效减轻ADD术后炎性反应药物（术中用药）Xu CE1,Zou CW,Zhang MY,Guo L.Ef
22、fects of high-dose ulinastatin on inflammatory response and pulmonary function in patients with type-A aortic dissection after cardiopulmonary bypass under deep hypothermic circulatory arrest.J Cardiothorac Vasc Anesth.2013 Jun;27(3):479-84.36例A型夹层病人随机分两组，治疗组，20,000 units/kg 乌司他丁(n=18)（麻醉诱导、主动脉阻断、主动
23、脉开放给予）。对照组0.9%盐水(n=18)结果大剂量乌司他丁可降低血浆炎性因子和白细胞弹力蛋白酶改善氧合指数缩短术后呼吸机治疗时间缩短ICU停留时间 药物（术中用药）Nishibe T1.etal.Protective effect of sivelestat sodium(Eraspol)on postoperative lung dysfunction in patients with type A acute aortic dissection:a pilot study.J Cardiovasc Surg(Torino).2008 Oct;49(5):627-31.12 例急性A型夹
24、层7例术中应用sivelestat sodium(弹性蛋白酶抑制药)5例为对照结果sivelestat sodium可显著改善术后氧合指数药物（术中用药）Niino T1,Hata M,Sezai A,Yoshitake I,Unosawa S,Fujita K,Shimura K,Osaka S,Minami K.Efficacy of neutrophil elastase inhibitor on type A acute aortic dissection Thorac Cardiovasc Surg.2010 Apr;58(3):164-8.60例急性A型夹层随机分两组实验组术中应用
25、sivelestat sodium(弹性蛋白酶抑制药)结果Sivelestat significantly reduced the postoperative decreases in AT III and platelet count in patients undergoing emergency surgery for AAD.sivelestat sodium可缩短术后机械通气时间总结 AAD围术期ALI的机制尚未完全明了 患者自身的易感因素 AAD导致的炎症反应 凝血纤溶系统激活 缺血再灌注损伤 手术本身、体外循环及深低温停循环技术 有关临床预防和治疗AAD围术期ALI措施的研究较少，需要进一步的深入研究
