围术期自体输血【-】

1、围术期自体输血首都医科大学北京友谊医院麻醉科 田 鸣2009.9.8 北京输血存在的两大问题血源性传染病和输血反应 我国乙肝病毒（HBV）感染人数达1.1亿，占总人口9%；90%丙肝由输血传播，输血后丙肝发病率高达10%-20%，特殊人群中丙肝病毒（HCV）携带者达70%；我国HIV感染者已超过84万，实际数？血源不足与滥用 我国年用血量超过1300吨，其中外科用血约占70%，临床不必要的输血占50%。输血原则安全、有效、节约围术期输血Perioperative Transfusion MedicineNon-Transfusion MethodsHemostasis (Surgical /

2、Medicine)Transfusion TriggerIndications for Blood TransfusionAutotransfusionPreoperative Autologous Donation (PAD)Acute Normovolemic Hemodilution (ANH) Intraoperative Autologous DonationRed Cell Salvage (CS)Minimize Allogeneic Transfusion过去二十年临床输血的改变Changes in red blood cell transfusion practice dur

3、ing the past two decadesA retrospective analysis, with the Mayo database, of adult patients undergoing major spine surgery1980 to 1985 early practice group; n = 6991995 to 2000 late practice group; n = 610Compared to the early practice group:所有术前的 Hb 浓度显著降低异体 RBC 输入显著减少，而自体输血明显增加no significant diffe

4、rence in major morbidity or mortality was observed between groupsWass CT, Transfusion. 2007;47(6):1022 USA无血外科的概念1. 不输血2. 自体输血3. 成分输血（异体）术前准备、手术技术麻醉、输血科管理医院多处室协调目的：减少异体输血掌握输血指征Transfusion Trigger:必须开始输血的时机：Hb/Hct 和 综合判断10/30 rules: Hb10g/dl；Hct30 % 一般情况下，达到了这个标准就不必继续输血出手术室、出院时Overtransfusion: 在任何时候当

5、输血使得 Hct36% 时，就认为是过度输血失血后不输血的手术死亡率 术前Hb水平 死亡率（%）Carson 1988 Hb Transfusion Trigger US 6g/dl：50岁，无心脏病和术后并发症 8g/dl：稳定性的心脏病，失血300ml10g/dl：老年人，术后有并发症，心肺代偿差Robertie：Int Anesthesiol Clin 28：197-204，199011g/dl（Hct33）：重危病人，强调维持适当的血容量比输血更重要Czer and Shoemaker：Optimal hematocrit value in critically ill postope

6、rative patients. Surg Gynecol Obstet 147: 363-368,1978卫生部输 血 指 南（2000年） Hb 100g/L 不必输血 Hb Risk治疗应当执行Benefit Risk治疗有理由执行需要补充特定的研究Benefit Risk治疗没有理由不执行需要补充广泛的研究Risk Benefit治疗不应当执行因为无益或有害Level A 多个 (3-5)人群的风险评估；一致的认识方向和明显的疗效。Recommendation that procedure or treatment is useful/effective Sufficient evid

7、ence from multiple randomized trials or meta-analyses Recommendation in favor of treatment or procedure being useful/effective Some conflicting evidence from multiple randomized trials or meta-analyses Recommendations usefulness/efficacy less well established Greater conflicting evidence from multip

8、le randomized trials or meta-analyses Recommendation that procedure or treatment not useful/effective and may be harmful Sufficient evidence from multiple randomized trials or meta-analyses Level B 有限 (2-3)人群的风险评估Recommendation that procedure or treatment is useful/effectiveLimited evidence from sin

9、gle randomized trial or non-randomized studies Recommendation in favor of treatment or procedure being useful/effectiveSome conflicting evidence from single randomized trial or non-randomized studies Recommendations usefulness/efficacy less well established Greater conflicting evidence from single r

10、andomized trial or non-randomized studies Recommendation that procedure or treatment not useful/effective and may be harmfulLimited evidence from single randomized trial or non-randomized studies Level C 极有限 (1-2)人群的风险评估Recommendation that procedure or treatment is useful/effectiveOnly expert opinio

11、n, case studies, or standard-of-care Recommendation in favor of treatment or procedure being useful/effectiveOnly diverging expert opinion, case studies, or standard-of-care Recommendations usefulness/efficacy less well established Only diverging expert opinion, case studies, or standard-of-care Rec

12、ommendation that procedure or treatment not useful/effective and may be harmful Only expert opinion, case studies, or standard-of-care Classification Scheme Used to Summarize of Clinical RecommendationsTransfusion TriggersClass IIaWith Hb 6 g/dL, RBC transfusion is reasonable, as this can be lifesav

13、ing. Transfusion is reasonable in most postoperative patients whose Hb=10 g/dL, but more evidence to support this recommendation is required. (Level of evidence C)Class IIITransfusion is unlikely to improve oxygen transport when Hb10 g/dL and is not recommended. (Level of evidence C)综合判断输血指征综合分析，因人而

14、异贫血持续的时间，血管内的容积手术的范围，大出血的可能性存在的合并症：如肺功能障碍，心输出量下降，心肌缺血，脑血管或外周循环疾病。综合判断：术中通过对术野的观察结合血标本的结果，对心肺功能的监测综合判断出每一病人所能接受的最低Hb值。Consensus Conference: Red Blood Cell Transfusion. JAMA, 1998, 260: 2700-2703取库血前是否测 Hb/Hct ？原则上应当测得 Hb/Hct 后再决定是否输血（取血）大多数（ 90%），常规都要执行但不绝对，结合临床（90%)在输血中或随后评估效果及进一步的需要量减少误判，节约血源和病人负担某

15、些例外是可能的 (20%措施：提高自体血应用量降低库血的应用量围术期自体输血的种类储存式 术前自体献血（ Preoperative Autologous Donation PAD）急性等容稀释(Acute Normovolemic Hemodilution ANH) （Intraoperative Autologous Donation）急性高容稀释(Acute Hypervolemic Hemodilution AHH)回收式（Blood Salvage BS）术中对自体血回收及回输术后对自体血回收及回输应当首选自体血避免血源传播性疾病避免输血的免疫反应降低对库血的需要量已备好或及时回收自体

16、血，有利于挽救血液质量高功能好术前自体献血Preoperative Autologous Donation PAD择期手术患者一般情况较好，Hb大于110g/L预计术中出血量超过循环血量15%稀有血型、配血困难；宗教信仰无心、肺、肾功能障碍无造血功能、凝血功能障碍无菌血症术前需多次采血，给病人带来不便可降低患者术前 Hb程序复杂，需要血库储存有成分的损耗（凝血因子等）血液保存时间有限，无法交互使用过期浪费的可能（50%），增加了费用采血和保存期有细菌污染的可能PAD 缺点 不常用急性等容稀释 (acute normovolemic hemodilution ANH)ANH常用是有效和最经济的自

17、体输血方法可以直接采集全血，也可通过专用设备单采红细胞采血的同时等量输入非细胞溶液（胶体或晶体液）室温保存，在手术室内输入Monk TG, Goodnough LT: Acute normovolemic hemodilution. Clin Orthop, 1998, 357:74-81血液稀释技术血液黏度的降低外周血管阻力的下降心输出量增加微循环改善组织氧摄取量的增加血红蛋白-氧亲和力降低血液稀释代偿血氧含量降低维持组织氧供病理生理学效应 血液稀释技术Gross 公式计算边采血边输液病人的采血量术前采血量（L） (采血前Hct -目标Hct) (采血前Hct+目标Hct)Gross JB:

18、 Estimating allowable blood loss: Corrected for dilution. Anesthesiology, 1983, 56: 577-580VL= EBV(HctO-HctF)/Hctave= 7体重（kg）2ANH 的方法麻醉后手术前采集自身血同时输入等量胶体液或3倍晶体液或不同比例的晶胶混合液稀释过程中保持血容量基本恒定术中血液有形成分丢失减少术终再将自体血反顺序回输Prospective RCT of ANH in major gastrointestinal surgeryAim : to assess the effects of ANH o

19、n allogeneic transfusion3unit-ANH n=78, no ANH n=82fewer patients in the ANH group experienced oliguria in the immediate postoperative period37/78 (47%) vs 55/82 (67%) (P=0.012).ANH 并不改变异体输血率术前 Hb 水平、术中失血量和输血规程是影响异体输血的关键因素compared with ASA-matched historical controls , the introduction of a transfus

20、ion protocol reduced the transfusion rate in colorectal patients from 136/333 (41%) to 37/138 (27%), P=0.004. Sanders G, Br J Anaesth. 2004;93(6):775 UK根据Hct变化程度，分为：轻度血液稀释：Hct30%中度血液稀释：Hct2029%血液稀释(hemodilution) 降低Hct、减少红细胞丢失中度血液稀释ASA推荐 Weiskopf , Transfusion 1995血液稀释扩展到Hct20%或更低的程度能显著提高对手术失血的耐受性可应对

21、相当大的手术失血量（4500ml）减少对异体输血的需要有经验的医师在“必需时”应用中度血液稀释ASA推荐 Weiskopf , Transfusion 1995方法为：1血液稀释在手术失血前完成；2.在达到目标Hct时开始回输采出的血液，而且回输的速度与手术失血等同以维持目标Hct；3.在自体血输完后再开始输异体血；4.维持正常的血容量。 ANH的适应证预计手术出血量5002000ml的患者合并有红细胞增多症的手术患者因宗教信仰不接受异体血液输入者血型罕见，术中需要输血者等血源紧张时，需要手术者ANH的禁忌证麻醉前评估为ASA 级及以上者严重贫血或凝血功能障碍的患者接受大面积植皮或体表整形手术

22、的患者因急性血液稀释可使手术创面的渗出量明显增加心功能不全或心脏内、外动静脉分流者有凝血病的病人术中没有大出血可能的病人血管条件差，采血困难者输血的时机尽可能在手术出血基本控制后输血大出血的当时快速补充血容量在全麻下允许短暂的Hct降低但要避免低血容量维持组织灌注大出血的当时输血增加了失血量加重了凝血障碍不可机械刻板，应酌情灵活处理术中自体血回收 CS可回收手术野失血量的 50-70%生理盐水洗涤的压积红细胞（ Hct 40-65% ）洗除了90%以上的血浆成分、血小板、细胞碎屑、游离Hb和活性物质（激活的凝血物质、血小板、补体，以及FDPs等）Cell Washing洗涤红细胞的优点能迅速、

23、及时地抢救病人红细胞质量高，2-3DPG，渗透脆性指数副作用小，(高钾、酸中毒、游离Hb及活性物质等)降低净失血量Saved red cell is a lucky cell!红细胞回收和其他降低围术期异体输血方法的效-价比Cost-effectiveness of CS and alternative methods of minimising perioperative allogeneic blood transfusionElectronic databases 1996-2004 for systematic reviews and 1994-2004 for economic ev

24、idence. Overall 668 studies Existing systematic reviews were updated with data from selected RCTs that involved adults scheduled for elective non-urgent surgeryCONCLUSIONS:The available evidence indicates that cell salvage may be a cost-effective method to reduce exposure to allogeneic blood transfu

25、sion. However, ANH may be more cost-effective than cell salvage.Davies L, Health Technol Assess. 2006 Nov;10(44):iii-iv, ix-x, 1-210, UK心血管外科的 CS心血管外科失血特点肝素化，创伤面积大，体外循环 “机械损伤、血液与空气的接触、以及血液与合成材料的接触，可导致溶血、血小板和白细胞功能丧失、补体激活、凝血功能紊乱以及炎症反应等”心脏手术的术野污染最小，红细胞回收率高，是最适合开展血液回收的手术类型。自体血回收的作用节约用血避免红细胞碎片及游离血红蛋白造成的损

26、害减少鱼精蛋白用量RED CELL AND PLATELET SAVINGClass IRoutine use of red cell saving is helpful for blood conservation in cardiac operations using CPB, except in patients with infection or malignancy. (Level of evidence A)Class IIIRoutine use of intraoperative platelet or plasmapheresis is not recommended for

27、 blood conservation during cardiac operations using CPB. (Level of evidence A)骨科手术的 CS骨科失血的特点骨科手术常从组织表面收集出血，失血是间断性吸出，血液和空气的结触较多，红细胞的损伤比较严重，因此红细胞的回收率相对较低血液中含有许多碎屑：骨、脂肪、和骨水泥碎片解决方法手控洗涤程序，降低泵转速自动慢速，大量生理盐水反复洗涤新型持续清洗系统CATS清洗后血液输血袋内静置1020min在回输前通过40m的滤器血液回收的缺点溶血影响RBC回收率凝血障碍稀释丢失丢失蛋白不可避免血液污染外伤后濒临死亡的大出血肿瘤细胞的播

28、撒当回收的浓缩红细胞量小于2000ml时 仅补充血浆代用品当回收的浓缩红细胞量大于2000ml时 超过2000ml的部分补以等量新鲜冰冻血浆当回收的浓缩红细胞量大于3000ml时，或血小板计数低于50109/L时补充适量的血小板大量输入回收血液时北京市术中血液回收利用质量管理及考核标准（试行 2009）术中血液回收利用适应证与禁忌证 人员与设备要求术中血液回收相关要求信息上报术中血液回收利用的考核指标低血容量治疗的一般程序1. 首先目标：循环容量的维持2. 第二目标：保持血氧携带能力3. 第三目标：恢复正常凝血状态和内环境稳定*97年美国麻醉年会(ASA)推荐小 结尽可能不输异体血、提高术前H

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39、P*ctJ#7oEV2izQ)duL!8pGW3kAR-fvM%9qHY4lCS+gxN&brIZ6mDU0hyP*ctJ#7oEV2izQ)duL!8pGW3kAR-fvM%9qHY4lCS+gxN&brIZ6mDU0hyP*ctJ#7oEV2izQ)duL!8pGW3kAR-fvM%aqHY4lCT+gxN&bsIZ6mDU1hyP*ctK#7oEV2jzQ)duL$8pGW3kBR-fvM%aqHY4lCT+gxN&bsIZ6mDU1hyP*ctK#7oEV2jzQ)duL$8pGW3kBR-fvM%aqHY4lCT+gxN&bsIZ6mDU1hyP*ctK#7oEV2jzQ)duL$8

40、pGX3kBR-fwM%aqHY5lCT+gxO&bsIZ6nDU1hyP(ctK#7oFV2jzQ)euL$8pGX3kBR-fwM%aqHY5lCT+gxO&bsIZ6nDU1hyP(ctK#7oFV2jzQ)euL$8pGX3kBR-fwM%aqHY5lCT+gxO&bsIZ6nDU1hyP(ctK!7oFV2jAQ)euL$9pGX3kBS-fwM%arHY5lCT0gxO&bsJZ6nDU1iyP(ctK!7oFV2jAQ)euL$9pGX3kBS-fwM%auL!8pFW3kAR-evM%9qHX4lCS+gwN&brIZ5mDU0hyO*ctJ#7nEV2izQ(duL!8pFW

41、3kAR-evM%9qHX4lCS+gwN&brIZ5mDU0hyO*ctJ#7nEV2izQ(duL!8pFW3kAR-evM%9qHX4lCS+gwN&brIZ6mDU0hyP*ctJ#7oEV2izQ)duL!8pGW3kAR-fvM%9qHY4lCS+gxN&brIZ6mDU0hyP*ctJ#7oEV2izQ)duL!8pGW3kAR-fvM%9qHY4lCS+gxN&brIZ6mDU0hyP*ctJ#7oEV2izQ)duL!8pGW3kAR-fvM%aqHY4lCT+gxN&bsIZ6mDU1hyP*ctK#7oEV2jzQ)duL$8pGW3kBR-fvM%aqHY4lCT+gx

42、N&bsIZ6mDU1hyP*ctK#7oEV2jzQ)duL$8pGW3kBR-fvM%aqHY4lCT+gxN&bsIZ6mDU1hyP*ctK#7oEV2jzQ)duL$8pGX3kBR-fwM%aqHY5lCT+gxO&bsIZ6nDU1hyP(ctK#7oFV2jzQ)euL$8pGX3kBR-fwM%aqHY5lCT+gxO&bsIZ6nDU1hyP(ctN&arIZ5mDT0hyO*csJ#7nEV1izQ(duK!8pFW3jAR-evM$9qHX4lBS+gwN&arIZ5mDT0hyO*csJ#7nEV1izQ(duK!8pFW3jAR-evM$9qHX4lBS+gwN&a

43、rIZ5mDT0hyO*csJ#7nEV2izQ(duL!8pFW3kAR-evM%9qHX4lCS+gwN&brIZ5mDU0hyO*ctJ#7nEV2izQ(duL!8pFW3kAR-evM%9qHX4lCS+gwN&brIZ5mDU0hyO*ctJ#7nEV2izQ(duL!8pFW3kAR-evM%9qHX4lCS+gwN&brIZ6mDU0hyP*ctJ#7oEV2izQ)duL!8pGW3kAR-fvM%9qHY4lCS+gxN&brIZ6mDU0hyP*ctJ#7oEV2izQ)duL!8pGW3kAR-fvM%9qHY4lCS+gxN&brIZ6mDU0hyP*ctJ#7oEV

44、2izQ)duL!8pGW3kAR-fvM%aqHY4lCT+gxN&bsIZ6mDU1hyP*ctK#7oEV2jzQ)duL$8pJ#6nEU1izP(dtK!8oFW2jAR)evL$9qGX4lBS+fwN&arIY5mDT0hxO*csJ#6nEV1izP(duK!8oFW3jAR)evM$9qGX4lBS+fwN&arIY5mDT0hxO*csJ#6nEV1izP(duK!8oFW3jAR)evM$9qGX4lBS+fwN&arIY5mDT0hxO*csJ#6nEV1izP(duK!8pFW3jAR-evM$9qHX4lBS+gwN&arIZ5mDT0hyO*csJ#7nEV1iz

45、Q(duK!8pFW3jAR-evM$9qHX4lBS+gwN&arIZ5mDT0hyO*csJ#7nEV1izQ(duK!8pFW3jAR-evM$9qHX4lBS+gwN&arIZ5mDT0hyO*csJ#7nEV2izQ(duL!8pFW3kAR-evM%9qHX4lCS+gwN&brIZ5mDU0hyO*ctJ#7nEV2izQ(duL!8pFW3kAR-evM%9qHX4lCS+gwN&brL$9pGX4kBS-fwN%arHY5mCT0gxO*bsJZ6nEU1iyP(dtK!7oFW2jAQ)evL$9pGX4kBS-fwN%arHY5mCT0gxO*bsJZ6nEU1iyP(d

46、tK!7oFW2jAQ)evL$9pGX4kBS-fwN%arHY5mCT09$Lve)QAj2WFo7!Ktd(Pyi1UEn6ZJsb*Oxg0TCm5YHra%Nwf-SBk4XGp9$Lue)QAj2VFo7!Ktc(Pyi1UDn6ZJsb&Oxg0TCl5YHra%Mwf-SBk3XGp9$Lue)QAj2VFo7!Ktc(Pyi1UDn6ZJsb&Oxg0TCl5YHra%Mwf-SBk3XGp9$Lue)QAj2VFo7!Ktc(Pyi1UDn6ZJsb&Oxg0TCl5YHqa%Mwf-RBk3XGp8$Lue)Qzj2VFo7#Ktc(Pyh1UDn6ZIsb&Oxg+TC

47、l5YHqa%Mwf-RBk3XGp8$Lue)Qzj2VFo7#Ktc(Pyh1UDn6ZIsb&Oxg+TCl5YHqa%Mwf-RBk3XGp8$Lue)Qzj2VFo7#Ktc(Pyh1UDn6ZIsb&Nxg+TCl4YHqa%Mvf-RBk3WGp8$Lud)Qzj2VEo7#Ktc*Pyh1UDm6ZIsb&Nxg+TCl4YHqa%Mvf-RBk3WGp8$Lud)Qzj2VEo7#Ktc*Pyh1UDm6ZIsb&Nxg+TCl4YHqa%Mvf-RBk3WGp8$Lud)Qzj2VEo7#Jtc*Pyh0UDm6ZIrb&Nxg+SCl4YHq9%Mvf-RAk3WGp8!

48、Lud)Qzi2VEo7#Jtc*Pyh0UDm6ZIrb&Nxg+SCl4YHq9%Mvf-RAk3WGp8!Lud)Qzi2VEo7#Jtc*Pyh0UDm6ZIrb&Nxg+SCl4YHq9%Mvf-RAk3WFp8!Lud(Qzi2VEn7#Jtc*Oyh0UDm5ZIrb&Nwg+SCl4XHq9%Mve-RAk3WFp8!Lud(Qzi2VEn7#Jtc*Oyh0UDm5ZIrb&Nwg+SCl4XHq9%Mve-RAk3WFp8!Lud(Qzi2VEn7#Jtc*Oyh0UDm5ZIrb&Nwg+SCl4XHq9$Mve-RAj3WFp8!Kud(Qzi1VEn7#Jsc*Oyh

49、0TDm5ZIra&Nwg+SBl4XHq9$Mve-RAj3WFp8!Kud(Qzi1VEn7#Jsc*Oyh0TDm5ZIra&Nwg+SBl4XHq9$Mve-RAj3WFp8!Kud(Qzi1VEn7#Jsc*Oyh0TDm5YIra&Nwf+SBl4XGq9$Mve)RAj3WFo8!Kud(Pzi1VEn6#Jsc*Oxh0TDm5YIra&Nwf+SBl4XGq9$Msb&Nxg+TCl4YHqa%Mvf-RBk3WGp8$Lud)Qzj2VEo7#Ktc*Pyh1UDm6ZIsb&Nxg+TCl4YHqa%Mvf-RBk3WGp8$Lud)Qzj2VEo7#Ktc*Pyh1UD

50、m6ZIsb&Nxg+TCl4YHqa%Mvf-RBk3WGp8$Lud)Qzj2VEo7#Jtc*Pyh0UDm6ZIrb&Nxg+SCl4YHq9%Mvf-RAk3WGp8!Lud)Qzi2VEo7#Jtc*Pyh0UDm6ZIrb&Nxg+SCl4YHq9%Mvf-RAk3WGp8!Lud)Qzi2VEo7#Jtc*Pyh0UDm6ZIrb&Nxg+SCl4YHq9%Mvf-RAk3WFp8!Lud(Qzi2VEn7#Jtc*Oyh0UDm5ZIrb&Nwg+SCl4XHq9%Mve-RAk3WFp8!Lud(Qzi2VEn7#Jtc*Oyh0UDm5ZIrb&Nwg+SCl4XHq9%

51、Mve-RAk3WFp8!Lud(Qzi2VEn7#Jtc*Oyh0UDm5ZIrb&Nwg+SCl4XHq9$Mve-RAj3WFp8!Kud(Qzi1VEn7#Jsc*Oyh0TDm5ZIra&Nwg+SBl4XHq9$Mve-RAj3WFp8!Kud(Qzi1VEn7#Jsc*Oyh0TDm5ZIra&Nwg+SBl4XHq9$Mve-RAj3WFp8!Kud(Qzi1VEn7#Jsc*Oyh0TDm5YIra&Nwf+SBl4XGq9$Mve)RAj3WFo8!Kud(Pzi1VEn6#Jsc*Oxh0TDm5YIra&Nwf+SBl4XGq9$Mve)RAj3WFo8!Kud(Pzi

52、1VEn6#Jsc*Oxh0TDm5YIra&Nwf+SBl4XGq9$Mve)RAj3WFo8!Kud(Pzi1UEn6#Jsb*Oxh0TCm5YIra%Nwf+SBk4XGq9$Lve)RAg+TCl4YHqa%Mvf-RBk3WGp8$Lud)Qzj2VEo7#Jtc*Pyh0UDm6ZIrb&Nxg+SCl4YHq9%Mvf-RAk3WGp8!Lud)Qzi2VEo7#Jtc*Pyh0UDm6ZIrb&Nxg+SCl4YHq9%Mvf-RAk3WGp8!Lud)Qzi2VEo7#Jtc*Pyh0UDm6ZIrb&Nxg+SCl4YHq9%Mvf-RAk3WFp8!Lud(Qzi2VE

53、n7#Jtc*Oyh0UDm5ZIrb&Nwg+SCl4XHq9%Mve-RAk3WFp8!Lud(Qzi2VEn7#Jtc*Oyh0UDm5ZIrb&Nwg+SCl4XHq9%Mve-RAk3WFp8!Lud(Qzi2VEn7#Jtc*Oyh0UDm5ZIrb&Nwg+SCl4XHq9$Mve-RAj3WFp8!Kud(Qzi1VEn7#Jsc*Oyh0TDm5ZIra&Nwg+SBl4XHq9$Mve-RAj3WFp8!Kud(Qzi1VEn7#Jsc*Oyh0TDm5ZIra&Nwg+SBl4XHq9$Mve-RAj3WFp8!Kud(Qzi1VEn7#Jsc*Oyh0TDm5YIra&

54、Nwf+SBl4XGq9$Mve)RAj3WFo8!Kud(Pzi1VEn6#Jsc*Oxh0TDm5YIra&Nwf+SBl4XGq9$Mve)RAj3WFo8!Kud(Pzi1VEn6#Jsc*Oxh0TDm5YIra&Nwf+SBl4XGq9$Mve)RAj3WFo8!Kud(Pzi1UEn6#Jsb*Oxh0TCm5YIra%Nwf+SBk4XGq9$Lve)RAj2WFo8!Ktd(Pzi1UEn6#Jsb*Oxh0TCm5YIra%Nwf+SBk4XGq9$Lve)RAj2WFo8!Ktd(Pzi1UEn6#Jsb*Oxh0TCm5YIra%Nwf+SBk4UDm6ZIrb&Nxg

55、+SCl4YHq9%Mvf-RAk3WGp8!Lud)Qzi2VEo7#Jtc*Pyh0UDm6ZIrb&Nxg+SCl4YHq9%Mvf-RAk3WFp8!Lud(Qzi2VEn7#Jtc*Oyh0UDm5ZIrb&Nwg+SCl4XHq9%Mve-RAk3WFp8!Lud(Qzi2VEn7#Jtc*Oyh0UDm5ZIrb&Nwg+SCl4XHq9%Mve-RAk3WFp8!Lud(Qzi2VEn7#Jtc*Oyh0UDm5ZIrb&Nwg+SCl4XHq9$Mve-RAj3WFp8!Kud(Qzi1VEn7#Jsc*Oyh0TDm5ZIra&Nwg+SBl4XHq9$Mve-RAj3WFp8!Kud(Qzi1VEn7#Jsc*Oyh0TDm5ZIra&Nwg+SBl4XHq9$Mve-RAj3WFp8!Kud(Qzi1VEn7#Jsc*Oyh0TDm5YIra&Nwf+SBl4XGq9$Mve)RAj3WFo8!Kud(Pzi1VEn6#Jsc*Oxh0TDm5YIra&Nwf+SBl4XGq9$Mve)RAj3WFo8!Kud(Pzi1VEn6#J