2012CRRT的局部枸橼酸抗凝(杜斌)

持续肾脏替代治疗的局部枸橼酸抗凝北京协和医院杜斌ICU中的急性肾脏功能衰竭*:BESTKidney患病率1738/29269(5.7%,95%CI5.5–6.0%)危险因素感染性休克(47.5%,95%CI45.2–49.5%)住院病死率60.3%(95%CI58.0–62.6%)*少尿(200ml/12hr)和(或)明显的氮质血症(BUN84mg/dL)UchinoS,KellumJA,BellomoR,etal.Acuterenalfailureincriticallyillpatients:amultinational,multicenterstudy.JAMA2005;294:813-818急性肾功能衰竭的定义:RIFLE标准GFR标准UO标准Risk肌酐增加x1.5或GFR降低25%UO0.5ml/kg/hrx6hrInjury肌酐增加x2或GFR降低50%UO0.5ml/kg/hrx12hrFailure肌酐增加x3或GFR降低75%UO0.3ml/kg/hrx24hr或无尿x12hrLoss持续ARF=肾脏功能完全丧失4周ESRD终末期肾病3月BellomoR,RoncoC,KellumJA,etal.Acuterenalfailure:definition,outcomemeasures,animalmodels,fluidtherapyandinformationtechnologyneeds:theSecondInternationalConsensusConferenceoftheAcuteDialysisQualityInitiative(ADQI)Group.CritCare2004;8:R204-R212ICU的急性肾脏损伤(AKI)OstermannM,ChangRWS.AcutekidneyinjuryintheintensivecareunitaccordingtoRIFLE.CritCareMed2007;35:1837-184335.8%17.20%11.00%7.60%0%20%40%60%AcuteKidneyInjury*FailureInjuryRisk急性肾功能衰竭的治疗(n=646)68.0%7.4%16.8%7.5%0%20%40%60%80%100%非透析IHDCRRTIHD+CRRT患者百分比(%)Perez-ValdiviesoJR,Bes-RastrolloM,MonederoP,etal.Prognosisandserumcreatininelevelsinacuterenalfailureatthetimeofnephrologyconsultation:anobservationalcohortstudy.BMCNephrology2007;8:14-22持续肾脏替代治疗管路寿命满足治疗要求降低治疗费用减少重新安装管路的护理时间18–30hr1.HoltAW,BiererP,GloverP,PlummerJL,BerstenAD.Conventionalcoagulationandthromboelastographparametersandlongevityofcontinuousrenalreplacementcircuits.IntensiveCareMed2002;28:1649-55.2.StefanidisI,HagelJ,FrankD,MaurinN.Hemostaticalterationsduringcontinuousvenovenoushemofiltrationinacuterenalfailure.ClinNephrol1996;46(3):199-205.3.KoxWJ,RohrU,WaurerH.Practicalaspectsofrenalreplacementtherapy.IntJArtifOrgans1996;19:100-5.4.TanHK,BaldwinI,BellomoR.Continuousveno-venoushaemofiltrationwithoutanticoagulationinhigh-riskpatients.IntensiveCareMed2000;26:1652-7.持续肾脏替代治疗的影响因素血管通路位置中心静脉导管:口径,管腔设计血流可靠性血滤管路设计透析膜的生物相容性护理人员的培训及专业技能抗凝效果持续肾脏替代的抗凝血滤滤器与管路的抗凝作用全身抗凝有害作用持续肾脏替代的抗凝选择基础疾病现有抗凝措施临床经验国内文献报告的抗凝方法抗凝方法病例数(%)单药抗凝普通肝素844(37.9)低分子肝素686(30.8)枸橼酸26(1.2)联合抗凝普通肝素+低分子肝素483(21.7)普通肝素+枸橼酸52(2.3)无抗凝137(6.1)CRRT时的肝素抗凝出血危险负荷剂量IU/kg维持剂量IU/kg/hrAPTTsecACTsec无危险性5010–2060250危险较小15–255–1045160–180危险较大102.5–530120肝素抗凝的优缺点优点最常用的抗凝方法临床方案成熟半衰期短过量时鱼精蛋白对抗缺点出血危险APTT与滤器寿命无关肝素诱导血小板缺乏(HIT)枸橼酸抗凝的原理局部枸橼酸抗凝的原理凝血过程需要游离钙参与枸橼酸螯合游离钙,补充钙离子可以恢复血库使用枸橼酸保存血液采用枸橼酸可以在RRT时进行局部抗凝:血液进入体外循环后即加入枸橼酸血液进入体内前补充游离钙体外循环对血液进行抗凝,体内血液正常通过测定游离钙监测抗凝肝素抗凝时的滤器中空纤维HofbauerR,MoserD,FrassM,etal.Effectofanticoagulationonbloodmembraneinteractionsduringhemodialysis.KidneyInt低分子肝素抗凝时的滤器中空纤维HofbauerR,MoserD,FrassM,etal.Effectofanticoagulationonbloodmembraneinteractionsduringhemodialysis.KidneyInt枸橼酸抗凝时的滤器中空纤维HofbauerR,MoserD,FrassM,etal.Effectofanticoagulationonbloodmembraneinteractionsduringhemodialysis.KidneyInt血滤终止的原因枸橼酸(n=36)肝素(n=43)管路凝血6(16.7%)23(53.5%)改为IHD1(2.8%)0血管通路问题2(5.6%)0管路断裂或渗漏1(2.8%)0管路打折1(2.8%)0转运至放射科或手术室8(22.2%)8(18.6%)滤器压力高1(2.8%)2(4.7%)其他原因16(44.4%)10(23.3%)KutsogiannisDJ,GibneyRTN,StolleryDetal.Regionalcitrateversussystemicheparinanticoagulationforcontinuousrenalreplacementincriticallyillpatients.KidneyInt2005;67:2361-2367滤器寿命的Cox风险比例模型分析HR95%CIP值枸橼酸0.3710.197–0.6990.002LOD评分1.2671.138–1.4110.001女性0.5240.314–0.8740.01AT-III水平0.2140.065–0.7120.01KutsogiannisDJ,GibneyRTN,StolleryDetal.Regionalcitrateversussystemicheparinanticoagulationforcontinuousrenalreplacementincriticallyillpatients.KidneyInt2005;67:2361-2367出血或输血的比例枸橼酸肝素相对危险度P值明确或隐性出血0.01(0–0.04)0.13(0.04–0.23)0.17(0.03–1.04)0.06输注RBC0.17(0.10–0.25)0.33(0.18–0.49)0.53(0.24–1.20)0.13输注FFP0.40(0.29–0.52)0.08(0.01–0.16)4.95(0.47–52.3)0.18KutsogiannisDJ,GibneyRTN,StolleryDetal.Regionalcitrateversussystemicheparinanticoagulationforcontinuousrenalreplacementincriticallyillpatients.KidneyInt2005;67:2361-2367CRRT时出血的多因素Poisson回归RR95%CIP值截距0.0010.00001–0.1740.008枸橼酸0.1370.020–0.9590.05LOD评分0.9240.571–1.4940.75AT-III水平6.6470.789–56.0030.08KutsogiannisDJ,GibneyRTN,StolleryDetal.Regionalcitrateversussystemicheparinanticoagulationforcontinuousrenalreplacementincriticallyillpatients.KidneyInt2005;67:2361-2367不同抗凝方法的滤器寿命KutsogiannisDJ,GibneyRTN,StolleryDetal.Regionalcitrateversussystemicheparinanticoagulationforcontinuousrenalreplacementincriticallyillpatients.KidneyInt2005;67:2361-2367枸橼酸局部抗凝方案枸橼酸局部抗凝图示RheaterACD-AVVPVPAUFBLDSAD葡萄糖酸钙枸橼酸局部抗凝方案说明血滤机常规预冲肝素盐水根据患者病情选择适当治疗模式CVVHCVVHDCVVHDF枸橼酸局部抗凝方案准备枸橼酸抗凝液血液保存液(I)600ml/袋广州华南医疗用品有限公司成分分子量含量(g)mmol枸橼酸三钠(二水)294.122.075枸橼酸(一水)210.148.038葡萄糖(一水)198.1724.5120加注射用水至1000mlRheaterACD-AVVPVPAUFBLDSAD葡萄糖酸钙枸橼酸局部抗凝方案准备输液泵将输液管路与血滤管路的动脉端相连接最接近患者处(血泵前)根据患者病情,设置血滤机的常规参数RheaterACD-AVVPVPAUFBLDSAD葡萄糖酸钙枸橼酸局部抗凝方案ACD-A初始泵速为血液流速(BFR)的2.0–2.5%泵速(ml/hr)=1.2–1.5xBFR(ml/min)例如BFR=120ml/minACD-A泵速=144–180ml/hrRheaterACD-AVVPVPAUFBLDSAD葡萄糖酸钙枸橼酸局部抗凝方案常规情况下选择前稀释方式RheaterACD-AVVPVPAUFBLDSAD葡萄糖酸钙枸橼酸局部抗凝方案置换液中不含钙RheaterACD-AVVPVPAUFBLDSAD葡萄糖酸钙常规置换液配方0.9%NS2000ml注射用水500ml5%NaHCO3125ml25%MgSO43ml10%CaGlu20ml15%KCl5ml50%GS总量枸橼酸局部抗凝方案准备10%葡萄糖酸钙溶液及注射器泵将输液管路连接至血滤管路静脉端葡萄糖酸钙溶液初始泵速为8.8–11.0ml/hr(ACD-A泵速的6.1%)RheaterACD-AVVPVPAUFBLDSAD葡萄糖酸钙枸橼酸局部抗凝方案:抗凝监测Q2hx4Q4hx