降低加护病房中心静脉导管相关血流感染率

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1、降低加護病房中心靜脈降低加護病房中心靜脈導管相關血流感染率導管相關血流感染率急護組林富美、蘇芳玉黃錦鳳、徐玉玫、張青蕙、何雲仙報告大綱前言EBN問題與步驟文獻探討文獻與本院情形之比較討論EBN過程評值未來計劃方向前言本院內外科加護病房共46床，其中內科15床主要收治內科重症病人，外科加護病房27床主要收治手術後重症病人及少數內科病人，急診加護病房7床收治內科為主外科為輔之重症病人。加護病房病人嚴重病況危急，抵抗力差且侵入性醫療措施裝置多，如呼吸治療管路、動靜脈導管、導尿管等等，這些裝置常是病源菌入侵人體的途徑。九十三年血流感染在內外科加護病房一直輪流佔第一、二位。九月份本院感染管制中心曾就加護

2、病房做院內感染流行調查，經卡方檢定結果發現院內感染個案增加情形，並無統計學上意義但結果發現血流感染人次之增加具統計上意義，而9位血流感染個案中，有8位有置入中心靜脈導管。 93年本院加護病房中心靜脈導管使用率平均為51.68 ，比起台灣醫療品質指標計劃（THIS）醫學中心數值相當（57.27 ）但中心靜脈導管相關血流感染率本院指標平均8.470/00 較THIS醫學中心與區域醫院之平均數值4.020/00 高出許多。喔? 中心靜脈導管相關血流感染率約為醫學中心與區域醫院的平均值的2倍問題在那兒？我們能做些什麼來降低呢？這不是專案改善嗎？我們是要EBN呢！STEP 1 Asking an ans

3、werable clinical questionn Practice reflectionn Decision making有什麼好問題第一次共識問題 中心靜脈導管護理使用甲消毒溶液會比 乙消毒溶液抗菌效果好嗎？ -查CDC的建議如何? -導管相關感染的因素很多 -很想與專案改善一魚兩吃呢！不如也先調查各家醫學中心現況CDC在有關消毒劑使用之建議Disinfect clean skin with appropriate antiseptic before insertion and at time of dressing change -2% chlorhexidine is preferr

4、ed.Do not apply organic solvents (acetone or ether) to skin before the insertion and at dressing change.Clean injection ports with 70% Alcohol or Iodophor before accessing.Allow antiseptics to remain on insertion site and air dry- povidoneiodine should be allowed to air dry for 2 minutes or longer.

5、各醫院中心靜脈導管護理 使用之消毒劑醫院名稱置入時皮膚消毒溶液 中心靜脈導管傷口護理溶液 忠孝優碘酒精、75%酒精75%酒精、優碘 台大優碘酒精 、75%酒精生理食鹽水、優碘 國泰優碘酒精、75%酒精生理食鹽水、優碘 馬偕優碘酒精、 75%酒精75%酒精、優碘 榮總優碘酒精 、75%酒精75%酒精、優碘酒精 新光優碘酒精 、75%酒精生理食鹽水、優碘 長庚優碘酒精 、75%酒精75%酒精、優碘酒精 三總優碘酒精 、75%酒精優碘CDC強調的合適的消毒劑，有建議較為合適的-2% Chlorhexidine。但同時強調使用消毒劑的注意事項。本院使用的消毒劑與大多數醫院雷同。預防導管相關血流感染之防

6、護，除了消毒劑外應有更多照護因子可介入。-主題可再想想-此次EBN主要目的利用EBN過程瞭解CDC預防血流導管相關感染防護措施的實證證據，是否能使中心靜脈導管相關血流感染率降低，以作為加護病房改善專案之參考。Decision making- 修訂留置中心靜脈導管病人照護標準規範EBN 問題： PICOCDC預防導管相關血流感染防護介入是否較 現行一般照護能降低加護病房中心靜脈導管相關血流感染率Intervention Problem or PatientOutcomeComparison改善專案 降低加護病房中心靜脈導管相關血流感染率Central venous catheter relate

7、d BSI防護感染主要原則CDC guidelineEducating&training:insert&maintaincatheterscareUsingmaximalsterilebarrierprecautionUsingchlorhexidineforskinantisepsisAvoidingroutinereplacementofCVCasastrategytopreventinfectionUsingantiseptic/antibioticimpregnatedshort-termCVCMonitoringperformanceindicatorAJIC,Vol.30(8).D

8、ecember 2002.476-489STEP 2 Search evidencesSearch strategy關鍵字: Infection control;ICU; CDC Central venous catheters; blood stream infection;catheter-related bloodstream infection 血流感染率；中心靜脈導管中文：4 篇HINT(MEDLINE)：73 篇ProQuest：13 篇PubMed：24 篇Cochrane：2 篇檢索結果資料太多怎麼篩選？先找Nursing standard及研讀CDC Guideline摘要再

9、分別往 hand hygiene ,antiseptics, insertion,maintain care, education-等焦點搜尋STEP 3 Critical appraisal the evidences名詞解釋中心導管（Central line）：為短期輸液或監測血液動力狀況而插入中央循環系統的暫時性血管內裝置或導管。 中心導管使用日數（Central line day）：在計算裝置使用日時，一個使用中心導管的加護病房病人算一個使用日。 裝置相關的感染(Device-associated infection)：是指一位加護病房的病患在感染發生前的48 小時內有使用一種醫療裝置

10、。而此感染不是在病患住進加護病房時已存有或有潛伏感染。中心導管相關之血流感染率必須符合全國院內感染監視手冊(NNIS)對實驗室證實的血流感染之標準標準1：一套或多套血液培養分離出致病菌且此致病菌與其它部位之感染無關。 標準2：發燒(38)、發冷或低血壓 (hypotension)等至少一項的臨床徵象標準3：一歲以下之嬰兒發燒(38)、體溫過低(37)、呼吸中止或心跳徐緩等至少一項臨床徵象且臨床徵象或症狀與陽性的實驗結果與其他部位的感染無關Quality of EvidenceI a-Meta-analysis of Randomized controlled trialsI b-One ran

11、domized controlled trialII a-One well designed controlled study without randomizationII b-One well designed quasi-experimental studyIII-Well designed non-experimental studies (comparative,correlation,other descriptive)IV- Expert committee reports,export opinions,care study文獻探討-EpidemiologyPrimary bl

12、oodstream infections are a frequent cause of morbidity and mortality in intensive care units worldwide. （CDC,2003）NNIS （1997）reports CVC-BSI rate of 5.20/00 in American, ICU rates of CVC-associated BSI range 2.9 to 11.3文獻探討-CRBSI造成的影響CRBSI increases in ICU Length of stay, total hospital cost, ICU co

13、st CRBSI increases risk of ICU mortalityOther predictors of ICU death were APACH III score（p.001）, age（p=.04）, GI surgery （p=.003）, alcohol abuse （p=.04）（Dimick,2001）Level I b CVC 感染危險因素分析1.輸液介面的污染2.穿刺部位的選擇3.頸內靜脈留置 4.不恰當的無菌屏障5.穿刺技術不佳2002美國CDC的導管相關感染的預防規範Skin antisepsisTitle: Chlorhexidine Compared w

14、ith Povidone-Iodine Solution for Vascular Catheter-Site Care A meta-analysis Purpose: Evaluate the efficacy of skin disinfection with Chlor.Gluco. compared with P-I solution in preventing catheter-related BSI.Data sources: Multiple computerized database(1966-2001),reference lists of identified artic

15、les.Study selection: RCT compared ,catheter-site. : MEDLINE, CINAHL,EBMASE, Cochrane Library , International Pharmaceutical Abstracts- Level I a續 出處:Ann Intern Med,V.136(11),2002Data Extraction: a standardized form , two reviewers abstracted data on study design , patient population, intervention, i

16、ncidence of CR-BSI from all included studies. Data Synthesis: 1.8 studies involving a total 4143 catheters met the criteria. 2.various catheter types were usedConclusion: Chlorhexidine gluconate reduced the risk for CR-BSI by 49% (95%CI,0.28-0.88)Education (Lobo et al., 2005) Impact of an education

17、program and policy changes on decreasing catheter-associated bloodstream infections in a MICU in Brazil Design: prospectively surveyed Intervention: highlight correct practices 1.CVC insertion, manipulation, and care/ monthly classes 2.Poster,discussion with staffLevel IIIEducation and training Resu

18、lt:Primary bloodstream infections 20 0/00 (phase 1, pre-intervention),11 0/00 (phase 2, post-intervention ) 120/00 (phase 3,follow-year) The adhesion to the overall CVC care policy improved significantly (p.01) Education （Berenholtz, 2004）Eliminating catheter-related bloodstream infections in the IC

19、U（16 beds SICU）Design: a prospective cohort study with concurrent controlIntervention:a quality improvement team, （1）education （2）creating a insertion cart（3）asking providers daily whether catheters could removed（4）a checklist to evidence-based guidelines for preventing CR-BSIs（5）empowering nurses t

20、o stop the catheter insertion procedure if a violation of the guidelinesLevel II aEducation and trainingIntervention: E: Surgical ICU（16床）, C: CVS ICU（15床）Results:（1）before, 62% followed infection control, after 100% （2）during, from 11.300/0 , first quarter 1998 to 0 00/0 , fourth quarter 2002; cont

21、rol ICU（15 beds CVS ICU）was from 5.7 to 1.6Education (Rosenthal et al, 2003)Effectofaninfectioncontrolprogramusingeducationandperformancefeedbackonrateofintravasculardevice-associatedbloodstreaminfectionsinICUsArgentinaDesign:Toascertaintheeffectofaninfectioncontrolprogramusingeducationandperformanc

22、efeedbackonICUIntervention:educationandtrainingforCDCandpreventionLevel II bEducation and trainingResults Phase I:baseline surveillance, 1219人數 ; Phase II:education, 586人數 Phase III: performance, 4140人數conclusion education and performance feedback result in a significant trend reduced of IVD-associa

23、ted BSIHand hygiene（Aiello et al.,2001）Assessment of tow hand hygiene regimens for intensive care unit personnelPurpose/Design: ProspectiverandomizedclinicaltrialfourconsecutiveweeksTocompareskinconditionandskinmicrobiologyamongICUpersonnelusingoneoftworandomlyassignedhandhygieneregimens:a2%chlorhex

24、idinegluconate:61%ethanolwithemollients(ALC)Level I b Hand hygiene Result: 50staffmembers(twoICU) 1.ParticipantsintheALCgrouphadsignificantimprovementsintheHandSkinAssessmentscoresatwk4(p=0.04)andinVisualSkinScalingscoresatwk3(p=0.01)and4(p=0.0005) 2. Thenwerenosignificantdifferencesinnumbersofcolon

25、yfromunitsbetweenparticipantsintheCGHorALCgroupatanytimeperiod.(193handcultures)Maximal sterile barrierTitle:Preventionofcentralvenouscatheter-relatedinfectionsbyusingmaximalsterileBarrierprecautionsduringinsertion.Objective:Toinvestigatedwhethertheuseofmaximalsterilebarrier(mask,cap,sterilegloves,g

26、own,andlargedrape)wouldlowertheriskofacquiringcatheterrelatedinfections.Source:InfectControlHospEpidemiol(1996,Apr.15)Level I bMaximal sterile barrier續 Design:RCT,GroupI-nontunneledcentercatheterinsertedundermaximalsterilebarrier.Gr.Iicontrolprecautions(sterilegloves&smalldrape)Atcatheterremoveorpos

27、tinsertion3ms.weretakencatheterculture&bloodculture.Maximal sterile barrier續Result:1.group1-176pts.;groupII-167pts2.group1-4catheterinf.;groupII-12catheterinf.P=0.03,chi-squaretest3.groupIIcatheter-relatedsepticemiaratewas6.3timeshigherGroupI(P=0.06,Fishersexacttest)4.67%ofgroupIIcatheterinf.-2msaft

28、erinsertion.25%ofgroupI-catheterinf.-thesameperiod.(p15個單位的細菌集落(C,25條，E,9條) 2.細菌集落情形(C,20%條，E,8條) 3.血流感染(C,6位，E,3位)Level I b antiseptic catheter結果 4.局部發炎(C,4條，E,0條) 5.細菌集落情形(C,20%條，E,8條) 6.抗感染安全尖端導管比控制組減少5倍的 感染率(C,4.9%，E,0.9%)Catheter-site care （Olivier, 1996）Prospective,randomizedtrialoftwoantisept

29、icsolutionsforpreventionofcentralvenousorarterialcathetercolonizationandinfectioninICUpatients（SICU）Design:Prospectiverandomizedclinicaltrial,E:0.25%chlorthexidinegluconate,0.25%benzalkoniumchlorideand4%benzylalcohol;C:10%povidoneiodine（betadine）Level I bCatheter-site care Outcome:therateofsignifica

30、ntcathetercolonizationandcatheter-relatedsepsisweresignificantlowerintheEgroup;therateofarterialcathetercolonizationwassignificantlowerintheEgroup,therateofarterialcatheter-relatedsepsiswassimilarfortwogroupConclusion:The0.25%chlorthexidinesolutionwassuperiortothe10%povidonesolutioninpreventioncathe

31、tercolonizationandcatheter-relatedsepsisduetoGram-postivebacteriaSurveillance for CRBSIs （Coopersmith, 2004）Theimpactofbedsidebehavioroncatheter-relatedbacteremiaintheICU（SICU）Design:beforeandaftereducationtrial;auditresult,abehavioralinterventionwasdesignedtoimprovecompliancewithevidence-basedguide

32、linesofCVCmanagementLevel I bSurveillance for CRBSIsResults:audit18m（1）documentingthedressingdate（11%to21%;p.001）,stopcockuse（70%to24%;p.99）maximalsterilebarrierprecautions（50%to80%;p=.29）（2）CRBSIsrate3.4to2.800/0（during15mafterintervention）穿刺部位選擇（Deshpande et al., 2005）Theincidenceofinfectiouscompl

33、icationsofcentralvenouscathetersatthesubclavian,internaljugular,andfemoralsitesinanintensivecareunitpopulation.PurposeTheobjectivewastoassesstheriskofcentralvenouscathetersinfectionwithrespecttothesiteofinsertioninanintensivecareunitpopulation.Thesubclavian,internaljugular,andfemoralsiteswerestudied

34、.Design:Prospective,observationalstudyLevel III穿刺部位選擇SubjectsAllpatientsweretriagedintotheICUbyon-sitecriticalcaremedicinefellows.Group1waspatientswithonecatheteratonesite.Group2waspatientswithcathetersatmultiplesites.Atotalof831centralvenouscathetersand4735catheterdaysin657patientswerestudied.穿刺部位選

35、擇ResultsIngroup1,（1）theincidenceofinfectionwassubclavian:0.881infections/1000catheterdays,internaljugular:0/1000,andfemoral:298/1000(p=0.2635)（2）Theincidenceofcolonizationwassubclavian:0.881colonization/1000catheterdays,internaljugular:2.00/1000,andfemoral:5.96/1000(p=0.1338)穿刺部位選擇Results-2Ingroup2,

36、therewasalsonostatisticallysignificantdifferenceintheincidenceofinfectionandcolonizationamongthethreeinsertionsites.Insertion site Selection （Jacques, 2001）Complicationsoffemoralandsubclavianvenouscatheterizationincriticalillpatients:arandomizedcontrolledtrialIntervention:randomizedcontrolledtrialas

37、signedtofemoralsite（n=145）orsubclaviansite（n=144）Level I bInsertion site SelectionResults:1.Femoralcatheterizationwasassociatedwithahigherincidencerateofoverallinfectiouscomplications（19.8vs4.5%;p.001;incidencedensityof20vs3.700/0）2.bloodstreaminfection4.4vs1.5%;p=.07;incidencedensityof4.5vs1.200/0）

38、3.thromboticcomplication（21.5vs1.9%;p14天）Maintain care72小時討論u最大無菌屏障是否還有需要加強的地方?裝備穿戴:帽子 口罩 手套 無菌衣 洞巾消毒範圍u是否要更改消毒劑？從三個成人加護病房開始宣導與執行評估執行成效後修訂規範再水平展開至全院討論u教育推行醫師：透過科務會議說明宣導 並藉由臨床技能中心加強技術訓練護士：透過晨會及病房會議宣導,擬定教育時間與課程u執行面的監測與分析技術操作過程的正確性u結果面感染率的改善 STEP 5 EvaluationSTEP 5 Evaluationu問題的適切性？！符合臨床實用性符合PICO的結構急需

39、要加以映證問題u文獻搜尋以BSI及ICU為關鍵字搜尋範圍太廣泛無法鎖定問題點以CDCGuideline為搜尋主軸隨即增加文獻完整性及焦點符合搜尋資料庫的廣度性 STEP 5 EvaluationSTEP 5 Evaluationu文獻評讀文獻評選多屬Level1&2可信度高u臨床應用性可供標準規範修訂之參考但無法馬上立竿見影需要持續推行與監控Risk factor of CRBSI宿主因素、住院天數、注射部位、皮膚準備、導管插入者經驗、導管材質、放置部位和留置時間、導管照護、使用輸液管路之數目、輸液成分、敷料更換頻率及其他部位感染等導管發現相關而未拔除導管者將有20%再發生菌血症，但拔除導管者

40、僅有3%再感染（郭, 2002）宿主因素，高齡、接受手術、疾病嚴重度高、WBC減少、接受類固醇或免疫抑制治療、心血管移植或缺損、嚴重營養不良等潛在性疾病未來計劃方向經本次EBN過程中學習到更多研究方法與設計，計劃未來可進一步做為本院 中心靜脈導管相關血流感染因素分析之探討Process recording成員調動攪亂了一江秋水線上作業當然優先囉！ 停了 忙- 忙- 忙猛然抬頭已接近報告時啊 ！強棒出擊得分囉！ 如期與大家分享謝謝聆聽 敬請指教!pXlUiQfNcK8H5E2A+x(u$rZnWkThPeMbJ7G4C1z-w&t!qYmVjRgOdL9I6F3B0y(v%s#oXlUiQfNb

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44、x*t$qZnVkShPdMaI7F4C0z)w&s!pXmUjRfOcL9H6E2B+y(u%r#oWlTiQeNbJ8G5D1A-x*t$qYnVkSgPdMaI7F3C0z)v&s!pXmUiRbK8G5D2A-x*t$qZnVkShPdMaI7F4C0z)w&s!pXmUjRfOcL9H6E3B+y(u%r#oWlTiQeNbJ8G5D1A-x*t$qYnVkSgPdMaI7F3C0z)v&s!pXmUiRfOcK9H6E2B+x(u%rZoWlThQeMbJ8G4D1A-w*t$qYnVjSgPdLaI7F3C0y)v&s#pXmUiRfNcK9H5E2B+x(u$rZoWkThQe

45、MbJ7G4D1z-w*t!qYmVjSgOdLaI6F3B0y)v%s#pXlUiRfNcK8H5E2A+x(u$rZnWkThPeMbJ7G4C1z-w&t!qYmVjRgOdL9I6F3B0y(v%s#oXlUiQfNbK8H5D2A+x*u$qZnWkShPeMaJ7F4C1z)w&t!pYmVjRgOcL9I6E3B0y(v%r#oXlTiQfNbK8G5D2A-x*u$qZnVkShPdMaJ7F4C0z)w&s!pYmUjRfOcL9H6E3B+y(u%r#oWlTiQeNbK8G5D1A-x*t$qZnVkSgPdMaI7F4C0z)v&s!pXmUjRfOcK9H6E2B+y

46、(u%rZoWlThQeNbJ8G4D1A-w*t$qYnVjSgPdLaI7F3C0y)v&s#pXmUiRfOcK9H5E2B+x(u%rZoWkThQeMbJ8G4D1z-w*t!qYnVjSgOdLaI6F3C0y)v%s#pXlUiRfNcK8H5E2A+x(u$rZnWkThPeMbJ7G4D1z-w&t!qYmVjSg9H5E2B+x(u%rZoWkThQeMbJ8G4D1z-w*t!qYnVjSgOdLaI6F3C0y)v%s#pXlUiRfNcK9H5E2A+x(u$rZoWkThPeMbJ7G4D1z-w&t!qYmVjSgOdL9I6F3B0y)v%s#oXlUiQfNc

47、K8H5D2A+x*u$rZnWkShPeMaJ7G4C1z)w&t!pYmVjRgOdL9I6E3B0y(v%s#oXlTiQfNbK8H5D2A-x*u$qZnWkShPdMaJ7F4C1z)w&s!pYmUjRgOcL9H6E3B+y(v%r#oWlTiQeNbK8G5D2A-x*t$qZnVkShPdMaI7F4C0z)w&s!pXmUjRfOcL9H6E2B+y(u%r#oWlThQeNbJ8G5D1A-w*t$qYnVkSgPdLaI7F3C0z)v&s#pXmUiRfOcK9H6E2B+x(u%rZoWlThQeMbJ8G4D1A-w*t!qYnVjSgPdLaI6F3C0y)v

48、&s#pXlUiRfNcK9H5E2A+x(u$rZoWkThPeMbJ7G4D1z-w*t!qYmVjSgOdLaI6F3B0y)v%s#pXlUiQfNcK8H5E2A+x*u$rZnWkThPeMaJ7G4C1z-w&t!pYmVjRgOdL9I6E3B0y(v%s#oXlUiQfNbK8H5D2A+x*u$qZnWkShPeMaJ7F4C1z)w&t!pYmUjRgOcL9I6E3B+y(v%r#oXlTiQeNbK8G5D2A-x*t$qZnVkShPdMaI7F4C0z)w&s!pYmUjRfOcL9H6E3B+y(u%r#oWlTiQeNbJ8G1z)w&t!pYmUjRgOcL

49、9I6E3B+y(v%r#oXlTiQeNbK8G5D2A-x*u$qZnVkShPdMaJ7F4C0z)w&s!pYmUjRfOcL9H6E3B+y(u%r#oWlTiQeNbJ8G5D1A-x*t$qYnVkSgPdMaI7F3C0z)v&s!pXmUiRfOcK9H6E2B+y(u%rZoWlThQeNbJ8G4D1A-w*t$qYnVjSgPdLaI7F3C0y)v&s#pXmUiRfNcK9H5E2B+x(u$rZoWkThQeMbJ7G4D1z-w*t!qYnVjSgOdLaI6F3C0y)v%s#pXlUiRfNcK8H5E2A+x(u$rZnWkThPeMbJ7G4C1z-w&

50、t!qYmVjRgOdL9I6F3B0y(v%s#oXlUiQfNcK8H5D2A+x*u$rZnWkShPeMaJ7G4C1z)w&t!pYmVjRgOcL9I6E3B0y(v%r#oXlTiQfNbK8G5D2A-x*u$qZnVkShPdMaJ7F4C0z)w&s!pYmUjRgOcL9H6E3B+y(v%r#oWlTiQeNbK8G5D1A-x*t$qZnVkSgPdMaI7F4C0z)v&slTiQfNbK8G5D2A-x*u$qZnWkShPdMaJ7F4C1z)w&s!pYmUjRgOcL9H6E3B+y(v%r#oWlTiQeNbK8G5D1A-x*t$qZnVkSgPdMaI

51、7F4C0z)v&s!pXmUjRfOcK9H6E2B+y(u%r#oWlThQeNbJ8G5D1A-w*t$qYnVkSgPdLaI7F3C0z)v&s#pXmUiRfOcK9H5E2B+x(u%rZoWkThQeMbJ8G4D1z-w*t!qYnVjSgPdLaI6F3C0y)v&s#pXlUiRfNcK9H5E2A+x(u$rZoWkThPeMbJ7G4D1z-w&t!qYmVjSgOdL9I6F3B0y)v%s#oXlUiQfNcK8H5E2A+x*u$rZnWkThPeMaJ7G4C1z-w&t!pYmVjRgOdL9I6E3B0y(v%s#oXlTiQfNbK8H5D2A-x*u$

52、qZnWkShPdMaJ7F4C1z)w&s!pYmUjRgOcL9I6E3B+y(v%r#oXlTiQeNbK8G5D2A-x*t$qZnVkShPdMaI7F4C0z%s#oXlTiQfNbK8H5D2A-x*u$qZnWkShPeMaJ7F4C1z)w&t!pYmUjRgOcL9I6E3B+y(v%r#oXlTiQeNbK8G5D2A-x*t$qZnVkShPdMaI7F4C0z)w&s!pXmUjRfOcL9H6E2B+y(u%r#oWlTiQeNbJ8G5D1A-x*t$qYnVkSgPdMaI7F3C0z)v&s!pXmUiRfOcK9H6E2B+x(u%rZoWlThQeMbJ8

53、G4D1A-w*t!qYnVjSgPdLaI7F3C0y)v&s#pXmUiRfNcK9H5E2B+x(u$rZoWkThQeMbJ7G4D1z-w*t!qYmVjSgOdLaI6F3B0y)v%s#pXlUiQfNcK8H5E2A+x*u$rZnWkThPeMbJ7G4C1z-w&t!qYmVjRgOdL9I6B+x(u$rZoWkThQeMbJ7G4D1z-w*t!qYmVjSgOdLaI6F3B0y)v%s#pXlUiRfNcK8H5E2A+x(u$rZnWkThPeMbJ7G4C1z-w&t!qYmVjRgOdL9I6F3B0y(v%s#oXlUiQfNbK8H5D2A+x*u$qZn

54、WkShPeMaJ7G4C1z)w&t!pYmVjRgOcL9I6E3B0y(v%r#oXlTiQfNbK8G5D2A-x*u$qZnVkShPdMaJ7F4C0z)w&s!pYmUjRfOcL9H6E3B+y(u%r#oWlTiQeNbK8G5D1A-x*t$qZnVkSgPdMaI7F4C0z)v&s!pXmUjRfOcK9H6E2B+y(u%rZoWlThQeNbJ8G4D1A-w*t$qYnVjSgPdLaI7F3C0z)v&s#pXmUiRfOcK9H5E2B+x(u%rZoWkThQeMbJ8G4D1z-w*t!qYnVjSgOdLaI6F3C0y)v%s#pXlUiRfNcK8H

55、5E2A+x(u$rZnWkThPeMbJ7G4D1z-w&t!qYmVjcK9H5E2B+x(u%rZoWkThQeMbJ8G4D1z-w*t!qYnVjSgOdLaI6F3C0y)v%s#pXlUiRfNcK9H5E2A+x(u$rZoWkThPeMbJ7G4D1z-w&t!qYmVjSgOdL9I6F3B0y)v%s#oXlUiQfNcK8H5D2A+x*u$rZnWkShPeMaJ7G4C1z-w&t!pYmVjRgOdL9I6E3B0y(v%s#oXlTiQfNbK8H5D2A-x*u$qZnWkShPdMaJ7F4C1z)w&s!pYmUjRgOcL9H6E3B+y(v%r#oWl

56、TiQeNbK8G5D2A-x*t$qZnVkShPdMaI7F4C0z)s#oXlTiQfNbK8H5D2A-x*u$qZnWkShPdMaJ7F4C1z)w&s!pYmUjRgOcL9I6E3B+y(v%r#oXlTiQeNbK8G5D2A-x*t$qZnVkShPdMaI7F4C0z)w&s!pXmUjRfOcL9H6E2B+y(u%r#oWlThQeNbJ8G5D1A-w*t$qYnVkSgPdMaI7F3C0z)v&s!pXmUiRfOcK9H6E2B+x(u%rZoWlThQeMbJ8G4D1A-w*t!qYnVjSgPdLaI6F3C0y)v&s#pXlUiRfNcK9H5E2B+x(u$rZoWkThQeMbJ7G4D1z-w*t!qYmVjSgOdLaI6F3B0y)v%s#pXlUiQfNcK8H5E2A+x*u$VjSgPdLaI6F3C0y)v&s#pXmUiRfNcK9H5E2B+x(u$rZoWkThQeMb